kisspeptin

Description of the potential effects of the substance Kisspeptin based on the literature. (This is not a product description, disclaimer at the bottom of the page)

Kisspeptin is a natural peptide hormone that plays a key role in controlling reproduction [1]. It acts as a master switch of the hypothalamic-pituitary-gonadal (HPG) axis, which is the system that regulates fertility in both men and women. This system begins in the hypothalamus of the brain, which releases a hormone called gonadotropin-releasing hormone (GnRH). GnRH then stimulates the pituitary gland to release two other hormones: luteinizing hormone (LH) and folliculotropic hormone (FSH). These two hormones are essential for sperm production in men and egg production in women.

Scientists discovered kisspeptin in 1996 in a cancer cell line [1, 2]. It was initially known to stop the spread of cancer. It was named KiSS-1 after the town of Hershey, Pennsylvania, famous for its chocolate kisses. Later, scientists discovered its major role in reproduction. The new research suggests that kisspeptin not only regulates fertility. It can also affect metabolism, mood, bone strength, heart health and even the ability of an embryo to implant in the uterus. Because of this wide range of effects, kisspeptin is currently being studied for therapies that improve both reproductive and overall health. Kisspeptin binds to a receptor called GPR54 (also known as KISS1R), which is found on GnRH-producing neurons in the brain [1, 2]. This binding triggers the release of gonadotropin-releasing hormone and starts the entire reproductive hormone chain. If kisspeptin or its receptor is not functioning, sexual maturation does not begin, as demonstrated in both human and animal studies. Neurons that produce kisspeptin also respond to signals from sex hormones such as estrogen and testosterone, and metabolic signals such as leptin and insulin. This allows kisspeptin to link fertility to overall energy balance and health.

Kisspeptin works together with other neurohormones such as GABA, neuropeptide Y and serotonin [1]. They all help adjust the timing and strength of reproductive hormone signals, depending on the different stages of reproduction. Kisspeptin itself is produced by the KiSS-1 gene, and the body converts it into smaller active fragments. These include kisspeptin-54, -14, -13 and -10, all of which have a similar tail end (C-terminal) that is needed for their action. The smallest but still effective fragment is called kisspeptin-10 or KP-10.

What does kisspeptin-10 do?

Kisspeptin-10 (KP-10), the smallest version of kisspeptin, exhibits potent biological activity. It can be administered externally to induce puberty or increase reproductive hormone levels. KP-10 activates the GPR54 receptor and increases levels of luteinizing hormone, folliculotropic hormone, estrogen and testosterone [1]. In humans, KP-10 is being studied as a potential drug for infertility and hormonal problems. It is also being used to help scientists understand how the brain controls reproduction. Kisspeptin may not only control fertility. New research shows that it can also help control weight, mood, bone health, heart function and pregnancy. For this reason, scientists are looking at kisspeptin as a possible treatment for both fertility and other health problems.

Kisspeptin-10 for men (based on human studies)

Kisspeptin-10 has been found to strongly affect the male reproductive system, stimulating the release of luteinizing hormone (LH) and, in some cases, increasing testosterone levels. In the first human clinical trial conducted by George et al (2011), healthy adult men were administered kisspeptin-10 intravenously as a single bolus or continuous infusion [3]. A single bolus dose of 1 µg/kg caused a threefold increase in LH levels within 30 minutes. It also caused a slight increase in folliculotropic hormone (FSH), but had no immediate effect on testosterone. Interestingly, the higher dose of 3 µg/kg had a weaker effect, suggesting that kisspeptin-10 does not have a linear dose-response curve. When it was administered continuously at a high dose of 4 µg/kg/h for 22.5 hours, it maintained elevated LH levels and caused a 44% increase in testosterone, with no signs of hormonal desensitization or reduced efficacy over time. The lower-dose infusion also raised LH levels and significantly increased both the frequency and strength of LH pulses. These results show that kisspeptin-10 increases LH levels in a dose-dependent manner and can raise testosterone levels with prolonged exposure, supporting its possible role in treating reproductive hormone deficiencies in men [3].

Additional studies have confirmed that kisspeptin-10 reliably raises LH levels in men regardless of age, but the testosterone response is age-dependent. Ullah et al (2019) tested a single intravenous dose of kisspeptin-10 (1 µg/kg) in healthy young, middle-aged and older men [4]. All age groups had a strong LH response, demonstrating that the hypothalamus and pituitary gland remain sensitive to kisspeptin with age. However, only the younger group experienced a significant increase in testosterone. This suggests that while the brain's response to kisspeptin remains intact with age, the testes become less sensitive to LH, possibly due to problems associated with aging Leydig cells. These findings suggest that kisspeptin-based therapies may work better in younger men with central (brain-related) endocrine disorders than in older men with testicular dysfunction [4].

In men with type 2 diabetes mellitus (T2DM) and mild hypogonadism, kisspeptin-10 has been shown to improve both LH pulsatility and testosterone levels. George et al (2013) conducted a two-part study comparing men with T2DM with healthy controls [7]. In the first part, both groups received an intravenous bolus of kisspeptin-10 at a dose of 0.3 μg/kg. This caused a significant increase in LH levels; from 5.5 to 13.9 IU / L in healthy men and from 4.7 to 10.7 IU / L in men with diabetes. The magnitude of the LH increase was similar in both groups. In the second part of the study, men with T2DM were given an 11-hour infusion of kisspeptin-10. LH levels rose significantly from 3.9 to 20.7 IU/L, and testosterone levels increased by 34% (from 8.5 to 11.4 nmol/L). In addition, the frequency of LH pulses increased, and the total amount of pulsatile LH secretion quadrupled. These results suggest that kisspeptin-10 may be a physiological alternative to testosterone therapy for the treatment of central hypogonadism in men with diabetes [7].

In another study, Jayasen et al (2015) directly compared the hormone-releasing effects of kisspeptin-10, kisspeptin-54 and gonadotropin-releasing hormone (GnRH) in healthy men [10]. Participants received intravenous infusions of each substance at different doses. Both kisspeptin-10 and kisspeptin-54 produced dose-dependent increases in LH and FSH. At the highest dose tested (1.0 nmol/kg/h), kisspeptin-10 increased LH area under the curve (AUC) to 10.8 h-IU/L, while kisspeptin-54 increased it to 14.4 h-IU/L. In comparison, GnRH produced a much higher LH production of 34.1 h-IU/L. Although kisspeptin was less potent than GnRH, it more accurately copies the body's natural hormonal signaling. This may make them more suitable for long-term treatment of functional hypogonadism or for use in assisted reproductive technologies, as they may carry a lower risk of receptor desensitization [10].

In a human study focused on gender differences and menstrual cycle phases, kisspeptin-10 showed different hormonal effects depending on gender and estrogen levels. Jayasena et al (2011) tested different doses of intravenous kisspeptin-10 in healthy male and female volunteers [11]. In men, doses starting at 0.3 nmol/kg caused a rapid and dose-dependent increase in LH; from about 4 IU/L to over 10 IU/L and ~40% increase in FSH, all within 30 minutes. However, women in the early follicular phase (low estrogen) showed no significant changes in LH or FSH, even after higher doses (up to 32 nmol/kg) or with different delivery methods. In contrast, during the pre-ovulatory phase (when estrogen is high), a dose of 10 nmol/kg of kisspeptin-10 led to an increase in LH of about 3 IU/l and an increase in FSH of about 1 IU/l. These results show that estrogen status controls the pituitary response to kisspeptin. The study suggests that kisspeptin-10 may help trigger gonadotropin release in men and women with high estrogen levels, but may be less effective in estrogen-deficient states, such as amenorrhea or menopause, unless combined with hormone priming [11].

Kisspeptin for women

Kisspeptin-10 restores reproductive function in refractory hyperprolactinemia. Millar et al (2017) tested kisspeptin-10 in two women with hyperprolactinemic amenorrhea who had stopped responding to dopamine agonist therapy [13]. Each woman underwent two 12-hour monitoring sessions: one with placebo and one with continuous infusion of kisspeptin-10. During the session with kisspeptin, LH levels tripled, FSH levels doubled, and estradiol and testosterone rose sharply. LH pulsatility also returned, showing activation of the reproductive axis. The effects were dramatic; LH increased by more than 200%, FSH by more than 100%, and estradiol increased 4-6 times, all in just 12 hours. Placebo caused no change. This proves that kisspeptin-10 can bypass the inhibitory effect of prolactin on the hypothalamus and may offer a new approach to restoring fertility in women whose lack of menstruation is refractory to standard treatment.

In women with polycystic ovary syndrome (PCOS), kisspeptin-10 was found to stimulate luteinizing hormone (LH) secretion even when neurokinin B (NKB) signaling was blocked. Skorupskaite et al (2020) studied ten women with PCOS who took the NK3 receptor antagonist MLE4901 orally for seven days [14]. On the last day, they received an intravenous infusion of kisspeptin-10. The NK3R blocker alone reduced both LH and folliculotropic hormone (FSH) levels and slowed LH pulses, confirming that NKB normally supports LH activity. However, infusion of kisspeptin-10 caused a strong increase in LH production, mass and frequency of LH pulses, even with blocked NKB. Compared to the NK3R antagonist alone, kisspeptin raised LH by more than 150%, and FSH by 40%. Normally, estradiol levels help predict how much LH increases after kisspeptin, but this relationship disappeared when NKB was blocked. These results show that kisspeptin can bypass the role of NKB and still increase LH release. For this reason, kisspeptin-10 may be helpful in treating PCOS, a condition often characterized by impaired LH signaling and ovulation problems [14].

In healthy premenopausal women exposed to estradiol, kisspeptin-10 was shown to restore the frequency of LH pulses, even when NKB signaling was blocked. Skorupskaite et al (2016) conducted a crossover study on 20 women who received the NK3R antagonist AZD4901 along with transdermal estradiol, mimicking hormonal growth before ovulation [15]. When kisspeptin-10 was administered during this phase, LH levels rose from about 3 IU/L to more than 16 IU/L by the end of the infusion and remained elevated for at least 16 hours. Kisspeptin also increased both the frequency of LH pulses and the mass of LH. FSH levels also increased. While the overall duration of LH elevation was shorter with NKB blockade, the stimulatory effect of kisspeptin remained strong. These results suggest that kisspeptin acts independently of NKB and may be useful in treating ovulatory problems in women who still have normal estrogen levels but impaired hypothalamic signaling [15].

What's more, George et al (2012) examined how different hormonal states affect women's response to kisspeptin-10 [17]. They studied 34 women from four groups: in the early follicular phase, postmenopausal, taking combined oral contraceptives (COCs) and using long-acting progestogen implants (IMPs). LH and FSH responses were measured after a single intravenous dose of kisspeptin-10. LH levels increased significantly in women in the follicular phase and those using IMPs, but not in COC users. The strongest response occurred in postmenopausal women, whose LH levels more than doubled and were the only group showing an increase in FSH. The increase in LH in postmenopausal women was 2.3 times greater than in the follicular group, and they also showed a significant increase in FSH. COC users had about 60% less LH response. These results show that low estrogen and progesterone levels increased the sensitivity of the reproductive system to kisspeptin [17]. This demonstrates the potential of kisspeptin-based treatment for conditions such as hypothalamic amenorrhea or menopause-related infertility, while also showing that hormonal contraceptives can suppress the kisspeptin response.

Defects in follicular kisspeptin and NKB signaling can lead to poor fertilization and embryo formation. Blasco et al (2020) examined the ovarian cells of 56 infertile women undergoing in vitro fertilization (IVF) [21]. These women had conditions such as advanced age, endometriosis or poor ovarian response. Their granulosa and cumulus cells were compared with cells from 30 healthy egg donors. Gene analysis showed that KISS1 mRNA was 52% lower in the granulosa cells of the infertile women, especially in the older patients. Moreover, the TAC3 and TACR3 genes, which are responsible for neurokinin B signaling, were up to 20 times lower in women with endometriosis and poor ovarian response. As a result, this large decrease in gene expression suggests that infertility may be related to impaired follicular signaling. Since kisspeptin and neurokinin B help regulate hormone production and oocyte development, such signaling defects could lead to poor fertilization and embryo formation. Therefore, the study suggests that targeting these pathways may help improve egg quality in older or infertile women.

Other health benefits (based on animal studies)

Kisspeptin-10 may help reverse bone mass loss caused by estrogen deficiency. In a study by Li et al (2024), they found that kisspeptin-10 protects bone in mice lacking the Kiss1, Gpr54 or Dusp18 genes [22]. These mice experienced rapid and severe bone mass loss, such as a 40% decrease in bone volume and density. However, when these mice received kisspeptin-10 or a bone-targeted version ((DSS)₆-Kp-10) for eight weeks, their bone density and structure returned to healthy levels. Mechanistically, the peptide activated GPR54 receptors on osteoclasts and recruited Dusp18, which in turn blocked the Src pathway responsible for bone breakdown. As a result, osteoclast activity decreased by 30-50%, and the bone-targeted version showed the best effects with minimal hormonal changes [22]. These findings suggest that kisspeptin-10 may be a safe therapy for osteoporosis associated with low estrogen or aging. In addition to its role in bone health, kisspeptin-10 also appears to affect brain circuits that regulate hunger. In particular, Orlando et al (2018) used a rat hypothalamic cell line to study this effect [23]. They found that high doses of kisspeptin-10 more than doubled the expression of the NPY gene, a major hunger-promoting signal. At the same time, levels of BDNF, which helps reduce appetite, decreased by 35%. In addition, levels of dopamine and serotonin decreased by 30-35%, while their breakdown products increased, indicating faster neurotransmitter turnover. These results suggest that kisspeptin-10 may increase hunger by increasing appetite signals and suppressing satiety signals. Therefore, it could potentially affect eating behavior and energy balance over time.

Kisspeptin-10 also affects fat cells, changing the way they grow, store fat and respond to hormones. According to Pruszyńska-Oszmałek et al (2017), kisspeptin-10 reduced adipocyte growth by 25-35% and blocked fat storage during development [24]. This was achieved by decreasing the expression of fat-forming genes such as PPAR-γ and C/EBP-β. Moreover, fat breakdown increased by 30%, and the production of enzymes such as perilipin and hormone-sensitive lipase more than doubled. In addition, kisspeptin-10 made fat cells less responsive to insulin and reduced glucose storage by 20-25%. Interestingly, leptin levels increased by 25%, which promotes satiety, but adiponectin decreased by 30%, which may signal inflammation. Overall, these results show that kisspeptin-10 pushes fat cells to burn fat, although the decrease in adiponectin suggests that long-term use may require caution.

Kisspeptin-10 may protect blood vessels in the brain, especially in the context of aneurysms. Yu et al (2025) tested this on mice with brain aneurysms. After four weeks of treatment, aneurysm size and inflammation were reduced by 40-60% [25]. Levels of MMP-9 and VEGF-A, which contribute to vascular damage, were also lower. Moreover, blood vessel walls remained intact, and the accumulation of immune cells was reduced. However, these benefits disappeared in mice lacking GPR54, showing that the effect depends on kisspeptin signaling. Further in vitro studies using human brain endothelial cells showed that kisspeptin-10 blocked abnormal blood vessel growth by downregulating Egr-1, a gene associated with inflammation. These findings suggest that kisspeptin helps protect blood vessel integrity, and the low levels of kisspeptin in patients with aneurysms suggest that it may serve as a useful biomarker. Therefore, kisspeptin-based therapies may offer a non-surgical approach to managing aneurysm progression or risk of rupture.

Kisspeptin-10 slows the aging of cartilage cells caused by inflammation. In particular, Qiu et al (2025) found that kisspeptin-10 helps protect cartilage cells (chondrocytes) from inflammation stress-induced aging [26]. In their study, mouse cartilage cells were treated with TNF-α to develop osteoarthritis. As a result, more than 55% cells showed signs of aging, and telomerase activity decreased by 45%. However, after administration of 100 nM kisspeptin-10, the percentage of aging cells decreased to 29%, and telomerase levels increased to 90% of normal. What's more, kisspeptin-10 increased the level of SIRT1 protein by 2.1 times and decreased the levels of aging-related proteins p53 and p21 by 40% and 55%, respectively. Importantly, these protective effects disappeared when SIRT1 was blocked, demonstrating that SIRT1 is crucial to the action of kisspeptin-10. In addition, the peptide restored GPR54 receptor levels, which had previously declined by 60% due to TNF-α. These results suggest that kisspeptin-10 may help delay cartilage damage in osteoarthritis by preserving youthfulness and cell function.

Kisspeptin-10 also exhibits antidepressant effects by acting on brain receptors. Serhatlioglu et al (2024) showed that kisspeptin-10 reduces behavioral symptoms of depression in rats [27]. When injected directly into the brain, kisspeptin-10 reduced immobility time in the forced swim test by 45%, indicating an improvement in mood. It is worth noting that blocking the kisspeptin receptor GPR54 abolished this effect. Moreover, when other brain signaling pathways, particularly α₂-adrenergic and serotonin 5-HT₂ receptors, were inhibited, the antidepressant effect decreased by 40%. This shows that these neurotransmitter systems also contribute to the mood-regulating effects of kisspeptin-10. Importantly, overall locomotor activity remained unchanged, indicating that the observed effects were not due to general arousal. These findings suggest that kisspeptin-10 may positively affect brain chemistry and may be useful in mood disorders involving hormonal and neurotransmitter imbalances. In addition, kisspeptin-10 rapidly increases male reproductive hormone levels. Thompson et al (2004) found that kisspeptin-10 strongly stimulates these hormones [28]. When injected into the brains of rats, luteinizing hormone (LH) increased by 400%, folliculotropic hormone (FSH) by 60%, and testosterone levels doubled; all in just one hour. A similar effect was observed with intravenous administration. Moreover, under laboratory conditions, kisspeptin-10 caused a 200-300% increase in GnRH release from the hypothalamus, but had no direct effect on hormone release from the pituitary. This clearly shows that kisspeptin-10 acts at the level of the hypothalamus, initiating the hormone cascade from above. Therefore, its rapid and specific action supports its potential use in the diagnosis and treatment of reproductive disorders such as delayed puberty and hypothalamic amenorrhea.

Moreover, kisspeptin-10 helps reduce oxidative damage in testicular tissue under hypothyroid conditions. In a study by Santos et al (2024), rats with long-term hypothyroidism experienced high oxidative stress and reduced antioxidant defense in the testes [29]. Treatment with kisspeptin-10 restored the antioxidant genes SOD1 and GPx1 to near normal levels. In addition, harmful compounds such as peroxynitrite were 50% reduced, and apoptosis in germ cells decreased. Although kisspeptin-10 did not restore the expression of unfolded protein response (UPR) genes, it still significantly reduced oxidative damage and cell death. As a result, this peptide may offer protective benefits for male fertility against thyroid dysfunction and oxidative stress.

Kisspeptin-10 can also protect the brain from oxidative stress caused by harmful chemicals. In a rat study in which brain damage was induced with L-methionine, which increases oxidative stress, treatment with kisspeptin-10 six hours later significantly reduced the damage [30]. Compared to untreated rats, those receiving the peptide showed less DNA fragmentation, 40-60% lower lipid peroxidation, twice the level of glutathione (GSH) and near-normal superoxide dismutase (SOD) activity. Conversely, untreated animals showed severe cell death and antioxidant depletion. Therefore, these results suggest that kisspeptin-10 helps restore redox balance and may provide neuroprotection against chemically induced oxidative brain damage.

In models of Parkinson's disease, kisspeptin-10 has also shown protective effects on the brain [31]. In a study using human nerve cells with toxic α-synuclein accumulation, kisspeptin-10 halved apoptosis, restored mitochondrial function and reduced α-synuclein clumps by about 30%. Interestingly, these protective effects persisted even after blocking the GPR54 receptor, indicating a receptor-independent mechanism. Therefore, this suggests that kisspeptin-10 can directly interfere with the accumulation of toxic proteins, making it a promising candidate for neuroprotection in Parkinson's disease. Kisspeptin-10 may also help during stroke. Specifically, in mice with cerebral ischemia-reperfusion injury, pretreatment with kisspeptin-10 reduced dopamine release in the brain striatum by nearly 40% [32]. Although this did not reverse oxidative damage or lipid changes, it significantly affected the behavior of glial cells and helped maintain chemical balance in the brain. Therefore, these results suggest that kisspeptin-10 may be useful in treating early brain damage and inflammation associated with stroke.

In addition, kisspeptin-10 may protect the reproductive system from oxidative stress. In a study on young rats, high doses of methionine caused testicular damage and disrupted hormone levels [33]. However, concurrent treatment with kisspeptin-10 preserved the structure of sperm-producing tissues and partially restored luteinizing hormone (LH) levels. In addition, it increased the activity of antioxidant enzymes, particularly SOD and catalase, and reversed gene suppression associated with oxidative stress. As a result, these results indicate that kisspeptin-10 can promote both puberty and fertility by protecting testicular health during oxidative challenges. Moreover, kisspeptin-10 protects male fertility from arsenic-induced damage. In a study involving adult male mice, prolonged exposure to arsenic led to testicular shrinkage, high oxidative stress and impaired semen quality [34]. When kisspeptin-10 was administered intermittently or continuously, oxidative damage was reduced by 40-60%. In particular, markers such as malondialdehyde and protein carbonyls decreased, while levels of antioxidant enzymes returned to baseline or exceeded normal. In addition, testosterone and fructose levels in semen plasma increased by 25-40%, and sperm count, motility and morphology improved. Histological analysis also revealed preserved seminal tubules and active sperm production. These results suggest that kisspeptin-10 may mitigate reproductive damage caused by toxic metals such as arsenic.

In addition, kisspeptin neurons are essential for female sexual behavior. In female mice, removal of kisspeptin neurons from the AVPV/PeN brain region abolished partner choice and lordosis posture, despite normal hormone levels [35]. It is noteworthy that these behaviors were restored after administration of KP-10 or light-induced activation of kisspeptin neurons. While sexual motivation was dependent on GPR54-GnRH signaling, the physical mating posture required nitric oxide from nNOS-positive neurons. Therefore, this shows that kisspeptin coordinates both neurological and physical aspects of reproductive behavior and may help treat conditions such as sexual motivation disorder or infertility in women. In addition, kisspeptin-10 protects the testes from chemotherapy-related injury. In rats treated with methotrexate, sperm quality deteriorated, oxidative stress increased, and the number of abnormal sperm doubled [36]. However, a 10-day regimen of kisspeptin-10 after treatment significantly reduced oxidative markers such as MDA, while sperm motility increased above 70% and deformed sperm decreased by 50%. The weight of reproductive organs, including seminal vesicles and caudal epididymides, was also restored. These results support the concept that kisspeptin-10 may protect male reproductive health during chemotherapy.

In aging, kisspeptin-10 promotes mitochondrial function in the brain. In aging rat and human brain cells, KP-10 triggered both autophagy and mitophagy through the CaMKKβ→AMPK→ULK1 pathway, acting independently of mTOR [37]. As a result, autophagic activity doubled, mitochondrial number increased by 35%, and complex I enzyme function increased by 40%. In addition, ATP levels increased by 25% in aging hippocampal tissue. These changes almost restored mitochondrial health to the levels observed in young rats. Therefore, given that mitochondrial decline plays a key role in neurodegenerative diseases such as Alzheimer's and Parkinson's, kisspeptin-10 may represent a potential therapeutic benefit in aging-related brain disorders (Mattam et al., 2021).

Similarly, kisspeptin-10 activates essential reproductive and growth hormones. In Holstein heifers, a single intravenous dose of 1 mg of kisspeptin-10 led to a noticeable increase in luteinizing hormone (LH) within 30 minutes, followed by a second peak in growth hormone (GH) after about 75 minutes [38]. In contrast, animals treated with saline showed no hormonal changes. This biphasic response illustrates the dual action of kisspeptin-10 on both the reproductive and growth axes. Therefore, it can be used to manage the onset of puberty and improve reproductive and growth performance.

In addition to systemic effects, kisspeptin-10 also exerts direct effects on the pituitary gland. In laboratory studies involving cells of the anterior pituitary lobe of young bulls and pigs, kisspeptin-10 stimulated LH release in a dose-dependent manner [39]. In bovine cells, only higher concentrations (1,000 and 10,000 nM) elicited a significant response. However, porcine cells responded to both 100 and 1,000 nM doses. Compared to GnRH, kisspeptin-10 induced about 30-50% of LH release. This indicates that kisspeptin-10 can directly affect gonadotropins without relying on hypothalamic GnRH, making it a valuable tool for reproductive control in livestock. However, short-term treatment with kisspeptin alone is insufficient to sustain sexual maturation. In a study on 28-week-old ewe lambs, hourly injections of kisspeptin-10 over a 24-hour period effectively increased LH and estradiol levels and even induced short-term ovulation in some animals [40]. However, luteal function was short-lived, and overall maturation time was not advanced compared to untreated controls. These findings indicate that although kisspeptin-10 can initiate reproductive signaling, it does not replace the full spectrum of maturation signals required for sustained maturation and fertility. Therefore, the normal development of sexual maturation still depends on other hormonal processes [40].

Kisspeptin-10 dose

Several studies have examined the effects of kisspeptin-10 using different doses, routes of administration and experimental forms. Intravenous (IV) bolus administration was one of the most common approaches. In healthy adult men, single intravenous doses ranged from 0.01 to 3.0 μg/kg, with the strongest LH response observed at 1 μg/kg. Interestingly, higher doses, such as 3 μg/kg, produced a weaker effect [3]. The same 1 μg/kg dose was also used to study the age-related hormonal response in men [4], while pediatric patients received a lower diagnostic dose of 0.313 μg/kg IV to assess the response of sexual maturation [8]. In continuous IV infusion protocols, kisspeptin-10 was administered at rates ranging from 1.5 to 4 μg/kg/h. For example, one study administered a bolus of 3 μg/kg followed by a continuous infusion at a rate of 1.5 μg/kg/h for 9 hours or 4 μg/kg/h for 22.5 hours, resulting in elevated LH and testosterone levels [3]. In men with type 2 diabetes, an 11-hour infusion at 4 μg/kg/h increased LH pulsatility and testosterone levels [7]. Similar infusion protocols have been used in women with PCOS or treated with estrogen, where 4 μg/kg/h for 7 hours significantly increased LH secretion and frequency, even in the presence of neurokinin B antagonism [14, 15]. In hyperprolactinemic women with amenorrhea, a 12-hour infusion of 1.5 μg/kg/h effectively restored gonadotropin secretion [13]. Short intravenous pulses have also been used in prepubertal ewe lambs, where hourly injections of 20 µg for 24 hours induced temporary ovulation, but did not induce permanent sexual maturation [40].

Also evaluated were subcutaneous (SC) administration. A single bolus of SC - a dose unspecified but consistent with previous endocrine protocols - was administered to healthy, lean and obese men, resulting in a significant increase in plasma irisin levels [9]. Another study tested SC doses of up to 32 nmol/kg in women in the early follicular phase, but no significant gonadotropin response was observed under low estradiol conditions [11].

Kisspeptin-10 as a diagnostic tool in men and women

In pediatric endocrinology, kisspeptin has shown value in identifying the cause of delayed sexual maturation. Chan et al (2018) studied 15 children with delayed or arrested puberty and found that the LH response to kisspeptin helped distinguish between the two conditions [5]. Some children had functional GnRH neurons and experienced temporary (constitutional) delayed puberty. These children responded to kisspeptin with an increase in LH similar to that seen in adults and showed nocturnal LH pulses, indicating the natural onset of puberty. Other children showed no LH response to kisspeptin, but responded to GnRH only after stimulation. This showed that while their pituitary glands were working, their GnRH neurons were not yet active. These results highlight how kisspeptin can be used to test the function of GnRH neurons and predict whether a child will begin puberty without treatment [5].

Kisspeptin-10 is also helpful in checking the recovery of the reproductive system in adults previously diagnosed with idiopathic hypogonadotropic hypogonadism (IHH). A study by Lippincott et al (2016) examined six men who had recovered from IHH [6]. Those who recovered normal testicular function responded to kisspeptin with an LH surge that acted like normal hormonal rhythms. On the other hand, men who relapsed into hypogonadism did not respond to kisspeptin, although their pituitary glands could still respond to GnRH. This suggests that the response to kisspeptin reflects the activity of GnRH neurons and may help confirm whether patients with conditions such as IHH or delayed puberty have truly recovered. This also supports the use of kisspeptin as a diagnostic tool to assess hormone recovery and fertility potential [6].

Kisspeptin-10 has also been used as a diagnostic tool in pediatric endocrinology. In a study by Chan et al (2020), 16 children with delayed puberty were given a single intravenous dose of kisspeptin-10 (0.313 μg/kg) [8]. Eight of these children responded to the hormone with a noticeable increase in LH (defined as ΔLH ≥ 0.8 mIU / ml), and all of them went through puberty naturally. In contrast, eight non-responders (ΔLH ≤ 0.4 mIU / ml) did not enter puberty before the age of 18. The kisspeptin test achieved 100% sensitivity and specificity (P = 0.0002) in predicting whether a child would go through puberty. It outperformed traditional diagnostic tools such as GnRH-stimulated LH tests, inhibin B levels, basal hormone measurements and even genetic markers. These findings suggest that kisspeptin-10 may replace or complement current methods of distinguishing between constitutional retardation and true hypogonadotropic hypogonadism in adolescents [8]. The metabolic effects of kisspeptin-10 have also been investigated, particularly its effect on irisin; a hormone released by muscle that is associated with improved metabolism and fat browning. Shamas et al (2019) studied this by administering kisspeptin-10 subcutaneously to lean men (mean BMI ≈ 23) and obese men (mean BMI ≈ 32) [9]. Both groups experienced a significant increase in blood irisin levels. In the lean participants, irisin levels increased from 59 to 96 ng/ml (an increase of 63%). In the obese participants, irisin increased from 41 to 76 ng/ml (an increase of 84%), and the peak was reached earlier than in the lean men. These results show that kisspeptin-10 can stimulate irisin release independently of body fat levels, suggesting its possible role in the treatment of obesity and metabolic disorders [9].

In addition, Sitticharoon et al (2021) investigated the role of kisspeptin in both metabolism and reproductive health [12]. They measured kisspeptin levels in the blood and cerebrospinal fluid (CSF) of 40 men undergoing elective surgery. Fasting blood samples showed that serum kisspeptin levels increased with body weight: 0.26 ng/ml in normal-weight men, 0.31 ng/ml in overweight men and 0.49 ng/ml in obese men (P < 0.01). This increase corresponded to similar increases in leptin levels and insulin resistance (measured by HOMA-IR). Serum kisspeptin positively correlated with BMI (r = +0.51), leptin (r = +0.53), fasting insulin (r = +0.46) and HOMA-IR (r = +0.44). Interestingly, kisspeptin levels were negatively correlated with LH (r = -0.35), but showed no significant association with total testosterone or blood glucose levels. It is noteworthy that kisspeptin was undetectable in cerebrospinal fluid samples, confirming that its source was peripheral rather than cerebral. The findings suggest that circulating kisspeptin may act as a metabolic signal related to adipose tissue and insulin resistance. Its negative association with LH may indicate an inhibitory or competitive effect, which may contribute to the low testosterone levels observed in obesity-related hypogonadism. Kisspeptin may therefore serve as both a biomarker and a potential target for the treatment of conditions that involve both metabolic and reproductive hormone imbalances [12].

In another study Al-Kaabi et al (2020) evaluated whether maternal plasma kisspeptin-10 (KP-10) could help detect preeclampsia (PE) in 100 women pregnant for the first time at 20 weeks' gestation [16]. Sixty of them developed preeclampsia, while 40 remained healthy. Blood samples were taken in both the second and third trimesters of pregnancy to measure KP-10 and reproductive hormones such as LH, FSH, β-hCG, estradiol and progesterone. KP-10 levels were consistently lower in women who developed preeclampsia at both time points. In the second trimester, KP-10 had an AUC of 0.662, with a sensitivity of 55% and a specificity of 87.5%, while performance improved in the third trimester (AUC = 0.747), with a sensitivity of 83.3% and a specificity of 67.5%. The hormonal profile showed lower KP-10 associated with higher estradiol in the second trimester and lower LH and FSH but higher β-hCG in the third; progesterone remained unchanged. Differences between the pre-eclampsia and control groups were marked. KP-10 achieved over 80% specificity in the second trimester and over 80% sensitivity in the third. However, the positive predictive values (22-33%) were low, meaning that KP-10 alone cannot confirm preeclampsia. However, its high negative predictive values (above 94%) suggest that it is reliable in ruling out preeclampsia [16]. These findings link low levels of KP-10 to hormonal changes in preeclampsia and support its use as an adjunctive tool in early screening, especially in combination with other markers. This also suggests a role for kisspeptin in the regulation of placental hormones during pregnancy.

Kisspeptin can promote placental development and uterine artery adaptation. Ziyaraa et al (2016) examined the role of KP-10 in fetal health and blood flow in 100 pregnant women after 20 weeks; 60 with preeclampsia (32 mild, 28 severe) and 40 healthy controls [18]. KP-10 levels were measured at mid- and late gestation, and fetal growth and placental blood flow were assessed by Doppler ultrasonography. KP-10 was significantly lower in cases of preeclampsia at both stages, and levels decreased as the severity of preeclampsia increased. In late pregnancy, KP-10 averaged 310 pg/ml in the control group, 215 pg/ml in mild PE and 145 pg/ml in severe preeclampsia. These reductions were significant, as KP-10 fell by 30% in mild and 55% in severe preeclampsia. A 100 pg/mL decrease in KP-10 predicted a 120 gram decrease in fetal weight. The hormone positively correlated with fetal weight (r = 0.4-0.45) and negatively with birth weight percentile and Doppler flow indices. These results show that KP-10 can help assess the severity of preeclampsia and detect fetal growth problems. The progressive decline suggests that kisspeptin may promote placental development and uterine artery adaptation, making it a useful marker for monitoring high-risk pregnancies.

Kisspeptin may also play a role in placental development. Katirci et al (2024) found that women with placenta previa had significantly lower levels of kisspeptin (KISS1) in both blood and placental tissue [19]. In these women, serum kisspeptin levels were half those of women with normal pregnancies. KISS1 gene expression in the placenta was reduced by 96%, while expression of the kisspeptin receptor (KISS1R) increased by 170%, presumably as a feedback response to compensate for low levels of the ligand. These changes became more extreme as pregnancy progressed. These findings suggest that poor kisspeptin activity may contribute to poor implantation and shallow trophoblast invasion, which are key features of placenta previa. Monitoring KISS1 and KISS1R levels in early pregnancy may help physicians identify women at risk for abnormal placentation and improve pregnancy outcomes [19].

Kisspeptin can provide additional information on implantation dynamics, especially when used together with hCG, but by itself it may not be reliable enough to monitor early pregnancy outcomes. Hu et al (2019) investigated whether serum kisspeptin could be a useful marker of implantation and early miscarriage in women undergoing frozen embryo transfer (FET) [20]. We measured levels of kisspeptin and hCG on days 14 and 21 after embryo transfer in 133 women. In successful pregnancies, kisspeptin levels doubled from day 14 to day 21, while they remained the same in biochemical pregnancies, suggesting that kisspeptin reflects the early activity of the developing placenta. Interestingly, women with twin pregnancies had the lowest kisspeptin levels on day 14, indicating an inverse relationship between kisspeptin and implantation rate. By day 21, kisspeptin levels had increased in all successful pregnancies, but hCG still better predicted the risk of miscarriage [20].

Final thoughts on kisspeptin-10

Kisspeptin-10 (KP-10), the smallest and most active part of the kisspeptin peptide family, offers a wide range of effects on both reproduction and overall health. Although its role in stopping the spread of cancer was first noted, it soon became clear that its main biological function lies in controlling the reproductive hormone system (hypothalamic-pituitary-gonadal axis). KP-10 effectively enhances key reproductive hormones such as LH, FSH, estrogen and testosterone, making it valuable in treating infertility, delayed puberty and hormone deficiencies in both men and women. Clinical studies have consistently shown that KP-10 can raise hormone levels in a dose-dependent manner, improving the strength and frequency of hormonal signals without a rapid loss of efficacy. This makes it a potential replacement for current hormone therapies, especially for conditions such as central hypogonadism and infertility. In men with diabetes and low testosterone levels, KP-10 may also provide a more natural way to restore hormonal balance. At the same time, its use in testing reproductive function, especially in children and adolescents, has proven to be very accurate and specific. However, the effects of KP-10 may vary depending on age, hormone levels and metabolic status. For example, while younger men typically see a strong increase in testosterone, older men may not respond as well, possibly due to age-related decline in testicular function. In women, the success of KP-10 is often dependent on estrogen levels, meaning that proper hormonal balance may be needed earlier for best results.

In addition to reproduction, early studies show that KP-10 may have other health benefits. Animal studies suggest it may play a role in metabolism, helping to regulate weight, blood sugar and energy consumption. It also appears to protect brain cells, improve mood, support heart health and even slow cartilage aging. These findings indicate its potential in areas such as obesity, neurodegenerative diseases and joint disease. In obstetrics, KP-10 is being studied as a marker for conditions such as pre-eclampsia and overall pregnancy health. While useful, it should still be used along with other tests for accurate diagnosis and risk assessment. In conclusion, Kisspeptin-10 is a potent and versatile peptide with great potential as both a therapeutic and diagnostic tool. Its natural hormone-stimulating mode of action, early safety record and broad activity in various systems make it a candidate for future medical use. However, further clinical trials and research are still needed to fully understand its long-term safety, ideal dosage and full range of benefits.

Frequently asked questions

• Where is Kisspeptin-10 naturally produced in the body?

The body produces kisspeptin in several places, notably in the hypothalamus in the brain. It is also found in the placenta, pancreas and reproductive organs (testes and ovaries), where it helps regulate hormonal signaling and development during puberty and pregnancy.

• What is the use of Kisspeptin-10 in medicine?

Kisspeptin-10 is being studied and used in a clinical setting to treat and diagnose diseases of the reproductive system. These include infertility, delayed or absent sexual maturation, and disorders in which LH and FSH levels are abnormally low. It helps stimulate the natural hormonal cascade necessary for ovulation, sperm production and hormonal balance.

• Can Kisspeptin-10 help those struggling with infertility?

Yes, Kisspeptin-10 can trigger natural hormone surges that promote fertility. In women, it can promote ovulation and improve egg quality, which is helpful in IVF procedures. In men, it can increase LH and testosterone levels, supporting sperm production.

• How is Kisspeptin-10 administered to patients?

The most common route of administration for Kisspeptin-10 is intravenous (IV) injection, either as a single bolus or continuous infusion. Subcutaneous (SC) injections have also been used in some studies. Intravenous methods tend to produce faster and more predictable hormonal responses.

• What are the usual dosages of Kisspeptin-10?

In clinical trials, single intravenous doses typically range from 0.01 to 3 micrograms per kilogram of body weight. With continuous infusion, doses of 1.5 to 4 micrograms per kilogram per hour have been shown to be effective in raising levels of hormones such as LH and testosterone.

• Are there any side effects of Kisspeptin-10?

Kisspeptin-10 is generally safe and well tolerated. Some people may experience mild symptoms such as redness, headache, nausea or minor irritation at the injection site, but serious side effects are rare.

• Is long-term use of Kisspeptin-10 safe?

Short-term use appears safe based on current studies. However, long-term safety has not been fully studied, so more research is needed to confirm how it works with repeated or long-term use.

• How does Kisspeptin-10 work biologically?

Kisspeptin-10 activates a receptor in the brain called GPR54, which signals the release of GnRH (gonadotropin-releasing hormone). This hormone then commands the pituitary gland to release LH and FSH, which are crucial for normal reproductive function.

• Does it directly raise testosterone levels?

Not directly. Kisspeptin-10 increases LH, which then stimulates the testes (Leydig cells) to produce testosterone. This chain reaction is particularly effective in younger men and those with functioning hormonal pathways.

• How quickly does Kisspeptin-10 take effect?

Kisspeptin-10 begins to act quickly. LH levels can begin to rise within 15 to 30 minutes after intravenous administration, and a rise in testosterone usually follows soon after.

• Does the body get used to Kisspeptin-10 (tachyphylaxis)?

Most studies show that Kisspeptin-10 remains effective even with repeated doses or continuous infusion over many hours. This suggests that it does not quickly lose its effect like some other hormone therapies.

• Can Kisspeptin-10 be given to children?

Yes, it has been used safely in children and adolescents in clinical settings, especially to determine if puberty is delayed or if there is a deeper hormone deficiency (hypogonadotropic hypogonadism).

• Is it also effective in the elderly?

Kisspeptin-10 can stimulate LH production in all age groups. However, the resulting increase in testosterone may be less in older men because the testes respond less effectively due to aging.

• How is Kisspeptin-10 used in diagnostics?

Doctors can use Kisspeptin-10 to check how well a person's GnRH neurons are working. By measuring LH levels after administration, it helps diagnose hormone-related problems, such as delayed sexual maturation or fertility problems.

• Is the kisspeptin test accurate?

Yes, especially in teenagers. Some studies show 100% accuracy in determining whether puberty will progress naturally, making it a powerful diagnostic tool.

• Can Kisspeptin-10 help with hormonal issues in diabetes?

Research suggests it may be useful in men with type 2 diabetes who have low testosterone levels. By improving the pulsation of LH, Kisspeptin-10 may in some cases help restore natural testosterone production.

• Can it help with weight loss or obesity?

Possible. One study found that Kisspeptin-10 increases levels of irisin, a hormone involved in fat burning and heat generation. This may indicate a future role in metabolic regulation or treatment of obesity.

• How is kisspeptin-10 linked to pregnancy problems such as pre-eclampsia?

Low levels of kisspeptin-10 during pregnancy are associated with a higher risk and severity of preeclampsia. Measuring kisspeptin can help identify women at risk at an early stage.

• Can kisspeptin-10 predict IVF success?

Although there is some evidence that higher levels of kisspeptin-10 may be associated with better embryo implantation, it is not as reliable as hCG in predicting pregnancy outcomes. More research is needed before it can be used routinely.

• Can I receive Kisspeptin-10 as a medication?

Currently, Kisspeptin-10 is not widely available as a commercial drug. It is mainly used in research settings or in specialized clinics dealing with reproductive or endocrine health.

Disclaimer

This article was written for educational purposes and is intended to raise awareness of the substance under discussion. It is important to note that the article is about the substance in general - it is not a description of a specific product (chemical reagent). We do not suggest using chemical reagents on humans - this is prohibited by law. For a product to be used for treatment, it must be registered as a drug. The information in the text is based on available scientific research and is not intended to serve as medical advice or promote self-medication. The reader should consult any health and treatment decisions with a qualified health professional.

References

1. Koysombat, Kanyada, Jovanna Tsoutsouki, Aaran H. Patel, Alexander N. Comninos, Waljit S. Dhillo, and Ali Abbara. "Kisspeptin and neurokinin B: roles in reproductive health." Physiological Reviews (2025).
2. Gottsch, M.L., Clifton, D.K., and Steiner, R.A., 2009 From KISS1 to kisspeptins: Historical perspective and suggested nomenclature. Peptides, 30(1), pp.4-9. https://www.com/science/article/pii/S0196978108002751
3. George, J. T., Veldhuis, J. D., Roseweir, A. K., Newton, C. L., Faccenda, E., Millar, R. P., & Anderson, R. A. (2011). Kisspeptin-10 is a potent LH stimulator and increases pulse rate in men. The Journal of clinical endocrinology and metabolism, 96(8), E1228-E1236. https://doi.org/10.1210/jc.2011-0089 .https://pmc.ncbi.nlm.nih.gov/articles/PMC3380939/
4. Ullah, H., Nabi, G., Zubair, H., Ullah, R., & Shahab, M. (2019). Age-dependent changes in reproductive axis response to kisspeptin-10 administration in healthy men. Andrology, 51(4), e13219. https://doi.org/10.1111/and.13219 https://pubmed.ncbi.nlm.nih.gov/30590872/
5. Chan, Y. M., Lippincott, M. F., Kusa, T. O., & Seminara, S. B. (2018). Divergent responses to kisspeptin in children with delayed sexual maturation. JCI insight, 3(8), e99109. https://doi.org/10.1172/jci.insight.99109 https://pmc.ncbi.nlm.nih.gov/articles/PMC5931121/
6. Lippincott, M. F., Chan, Y. M., Delaney, A., Rivera-Morales, D., Butler, J. P., & Seminara, S. B. (2016). Kisspeptin Responsiveness Signals Emergence of Reproductive Endocrine Activity: Implications for Human Puberty. The Journal of clinical endocrinology and metabolism, 101(8), 3061-3069. https://doi.org/10.1210/jc.2016-1545 .https://pmc.ncbi.nlm.nih.gov/articles/PMC4971332/
7. George, J. T., Veldhuis, J. D., Tena-Sempere, M., Millar, R. P., & Anderson, R. A. (2013). Exploring the pathophysiology of hypogonadism in men with type 2 diabetes: kisspeptin-10 stimulates serum testosterone and LH secretion in men with type 2 diabetes and mild biochemical hypogonadism. Clinical endocrinology, 79(1), 100-104. https://doi.org/10.1111/cen.12103 .https://pubmed.ncbi.nlm.nih.gov/23153270/
8. Chan, Y. M., Lippincott, M. F., Sales Barroso, P., Alleyn, C., Brodsky, J., Granados, H., Roberts, S. A., Sandler, C., Srivatsa, A., & Seminara, S. B. (2020). Use of kisspeptin to predict pubertal outcomes in adolescents with delayed puberty. The Journal of clinical endocrinology and metabolism, 105(8), e2717-e2725. https://doi.org/10.1210/clinem/dgaa162 https://pmc.ncbi.nlm.nih.gov/articles/PMC7282711/
9. Shamas, S., Rani, S., Afsheen, S., Shahab, M., Ejaz, R., Sadia, H., Khan, L., Rehman, T. U., Roshan, S., & Mayo, A. (2019). CHANGES IN IRISIN RELEASE IN RESPONSE TO PERIPHERAL ADMINISTRATION OF KISSPEPTIN-10 IN HEALTHY AND OBESE ADULT MEN. Acta endocrinologica (Bucharest, Romania: 2005), 15(3), 283-288. https://doi.org/10.4183/aeb.2019.283 https://pubmed.ncbi.nlm.nih.gov/32010344/
10. Jayasena, C. N., Abbara, A., Narayanaswamy, S., Comninos, A. N., Ratnasabapathy, R., Bassett, P., Mogford, J. T., Malik, Z., Calley, J., Ghatei, M. A., Bloom, S. R., & Dhillo, W. S. (2015). Direct comparison of the effects of intravenous kisspeptin-10, kisspeptin-54, and GnRH on gonadotropin secretion in healthy men. Human reproduction (Oxford, England), 30(8), 1934-1941. https://doi.org/10.1093/humrep/dev143 .https://pubmed.ncbi.nlm.nih.gov/26089302/
11. Jayasena, C. N., Nijher, G. M., Comninos, A. N., Abbara, A., Januszewki, A., Vaal, M. L., Sriskandarajah, L., Murphy, K. G., Farzad, Z., Ghatei, M. A., Bloom, S. R., & Dhillo, W. S. (2011). Effects of kisspeptin-10 on reproductive hormone release exhibits sexual dimorphism in humans. The Journal of clinical endocrinology and metabolism, 96(12), E1963-E1972. https://doi.org/10.1210/jc.2011-1408 https://pubmed.ncbi.nlm.nih.gov/21976724/
12. Sitticharoon, C., Mutirangura, P., Chinyoti, T., Iamaroon, A., Triyasunant, N., Churintaraphan, M., Keadkraichaiwat, I., Maikaew, P., & Sririwichitchai, R. (2021). Associations of serum kisspeptin levels with metabolic and reproductive parameters in men. Peptides, 135, 170433. https://doi.org/10.1016/j.peptides.2020.170433 https://pubmed.ncbi.nlm.nih.gov/33129892/
13. Millar, R. P., Sonigo, C., Anderson, R. A., George, J., Maione, L., Brailly-Tabard, S., Chanson, P., Binart, N., & Young, J. (2017). Hypothalamic-pituitary-ovarian axis reactivation by kisspeptin-10 in hyperprolactinemic women with chronic amenorrhea. Journal of the Endocrine Society, 1(11), 1362-1371. https://doi.org/10.1210/js.2017-00328 https://pubmed.ncbi.nlm.nih.gov/29264460/.
14. Skorupskaite, K., George, J. T., Veldhuis, J. D., Millar, R. P., & Anderson, R. A. (2020). Interactions of kisspeptin and neurokinin B in modulating gonadotropin secretion in women with polycystic ovary syndrome. Human reproduction (Oxford, England), 35(6), 1421-1431. https://doi.org/10.1093/humrep/deaa104 https://pmc.ncbi.nlm.nih.gov/articles/PMC7316500/
15. Skorupskaite, K., George, J. T., Veldhuis, J. D., Millar, R. P., & Anderson, R. A. (2016). Interactions between neurokinin B and kisspeptin in mediating estrogen feedback in healthy women. The Journal of clinical endocrinology and metabolism, 101(12), 4628-4636. https://doi.org/10.1210/jc.2016-2132 https://pmc.ncbi.nlm.nih.gov/articles/PMC5155690/.
16. Al-Kaabi, M. A., Hamdan, F. B., & Al-Matubsi, H. (2020). Maternal plasma levels of kisspeptin-10 in pregnant women with pre-eclampsia and its association with changes in their reproductive hormones. The journal of obstetrics and gynaecology research, 46(4), 575-586. https://doi.org/10.1111/jog.14208 https://pubmed.ncbi.nlm.nih.gov/32045961/
17. George, J. T., Anderson, R. A., & Millar, R. P. (2012). Stimulation by kisspeptin-10 of gonadotropin secretion in women is modulated by sex steroid feedback. Human reproduction (Oxford, England), 27(12), 3552-3559. https://doi.org/10.1093/humrep/des326 https://pubmed.ncbi.nlm.nih.gov/22956346/
18. Ziyaraa, M. A., Hamdan, F. B., & Mousa, L. R. (2016). Correlation of kisspeptin-10 levels and fetal well-being in patients with preeclampsia. Taiwanese journal of obstetrics & gynecology, 55(6), 840-846. https://doi.org/10.1016/j.tjog.2015.10.028 https://pubmed.ncbi.nlm.nih.gov/28040130/.
19. Katirci, Y., Kocaman, A., & Ozdemir, A. Z. (2024). Kisspeptin expression levels in patients with placenta previa: A randomized study. Medicine, 103(28), e38866. https://doi.org/10.1097/MD.0000000000038866 https://pmc.ncbi.nlm.nih.gov/articles/PMC11245181/
20. Hu, K. L., Zhang, Y., Yang, Z., Zhao, H., Xu, H., Yu, Y., & Li, R. (2019). Predictive value of serum kisspeptin concentration at 14 and 21 days after transfer of frozen thawed embryos. Reproductive biomedicine online, 39(1), 161-167. https://doi.org/10.1016/j.rbmo.2019.03.202 https://pubmed.ncbi.nlm.nih.gov/31230668/
21. Blasco, V., Pinto, F. M., Fernández-Atucha, A., González-Ravina, C., Fernández-Sánchez, M., & Candenas, L. (2020). Female infertility is associated with altered expression of neurokinin B/neurokinin B and kisspeptin/cisspeptin receptor systems in ovarian granulosa and cumulus cells. Fertility and Sterility, 114(4), 869-878. https://doi.org/10.1016/j.fertnstert.2020.05.006 https://pubmed.ncbi.nlm.nih.gov/32811673/.
22. Li, Z., Yang, X., Fu, R., Wu, Z., Xu, S., Jiao, J., Qian, M., Zhang, L., Wu, C., Xie, T., Yao, J., Wu, Z., Li, W., Ma, G., You, Y., Chen, Y., Zhang, H. K., Cheng, Y., Tang, X., Wu, P., ... Xiao, J. (2024). Binding of kisspeptin-10 to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated Src phosphorylation. Nature communications, 15(1), 1300. https://doi.org/10.1038/s41467-024-44852-9 https://pubmed.ncbi.nlm.nih.gov/38346942/
23. Orlando, G., Leone, S., Ferrante, C., Chiavaroli, A., Mollica, A., Stefanucci, A., Macedonio, G., Dimmito, M. P., Leporini, L., Menghini, L., Brunetti, L., & Recinella, L. (2018). Effects of kisspeptin-10 on hypothalamic neuropeptides and neurotransmitters involved in appetite control. Molecules (Basel, Switzerland), 23(12), 3071. https://doi.org/10.3390/molecules23123071 https://pubmed.ncbi.nlm.nih.gov/30477219/
24. Pruszyńska-Oszmałek, E., Kolodziejski, P. A., Sassek, M., & Śliwowska, J. H. (2017). Kisspeptin-10 inhibits proliferation and regulates lipolysis and lipogenesis in 3T3-L1 cells and isolated rat adipocytes. Endocrine, 56(1), 54-64. https://doi.org/10.1007/s12020-017-1248-y https://pubmed.ncbi.nlm.nih.gov/28194651/
25. Yu, H., Xie, M., Liufu, X., Xu, Y., & Chen, L. (2025). Kisspeptin-10 prevents the development of cerebral aneurysms by reducing Egr-1 expression. CNS neuroscience & therapeutics, 31(5), e70413. https://doi.org/10.1111/cns.70413 https://pubmed.ncbi.nlm.nih.gov/40384564/
26. Qiu, J., Chen, G., Peng, G., Qu, G., Ren, T., & Deng, J. (2025). Kisspeptin-10 protects against TNF-α-induced chondrocyte aging through SIRT1/p53/p21 signaling. Journal of biochemical and molecular toxicology, 39(6), e70298. https://doi.org/10.1002/jbt.70298 https://pubmed.ncbi.nlm.nih.gov/40400312/
27. Serhatlioglu, I., Kacar, E., Yardimci, A., Ulker Ertugrul, N., Bulmus, O., Ercan, Z., & Kelestimur, H. (2024). The antidepressant effect of kisspeptin-10 is reversed by the kisspeptin antagonist peptide 234 in male rats. Cellular and molecular biology (Noisy-le-Grand, France), 70(10), 91-97. https://doi.org/10.14715/cmb/2024.70.10.13 https://pubmed.ncbi.nlm.nih.gov/39605118/
28. Thompson, E. L., Patterson, M., Murphy, K. G., Smith, K. L., Dhillo, W. S., Todd, J. F., Ghatei, M. A., & Bloom, S. R. (2004). Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic-pituitary-gonadal axis. Journal of neuroendocrinology, 16(10), 850-858. https://doi.org/10.1111/j.1365-2826.2004.01240.x https://pubmed.ncbi.nlm.nih.gov/15500545/.
29. Santos, L. C., Dos Anjos Cordeiro, J. M., Cunha, M. C. D. S. G., Santos, B. R., Oliveira, L. S., da Silva, A. L., Barbosa, E. M., Niella, R. V., de Freitas, G. J. C., Santos, D. A., Serakides, R., Ocarino, N. M., Borges, S. C., de Lavor, M. S. L., & Silva, J. F. (2024). Kisspeptin-10 improves testicular redox status but does not alter the unfolded protein response (UPR), which is reduced by hypothyroidism in a rat model. International Journal of Molecular Sciences, 25(3), 1514. https://doi.org/10.3390/ijms25031514 https://pubmed.ncbi.nlm.nih.gov/38338793/
30. Akkaya, H., Kilic, E., Dinc, S. E., & Yilmaz, B. (2014). Subacute effects of kisspeptin-10 on L-methionine-induced neuronal damage in rats. Journal of biochemical and molecular toxicology, 28(8), 373-377. https://doi.org/10.1002/jbt.21573 https://pubmed.ncbi.nlm.nih.gov/24863683/.
31. Simon, C., Soga, T., & Parhar, I. (2023). Kisspeptin-10 attenuates α-synuclein-mediated mitochondrial apoptosis in SH-SY5Y-derived neurons through a kisspeptin receptor-independent manner. International Journal of Molecular Sciences, 24(7), 6056. https://doi.org/10.3390/ijms24076056 https://pubmed.ncbi.nlm.nih.gov/37047030/.
32. Akkaya, H., Sümer, E., Kutlu, S., Solak, H., & Yılmaz, B. (2022). What is the protective effect of anterograde administration of kisspeptin-10 against striatal ischemia/reperfusion injury in mice? Turkish Journal of Medical Sciences, 52(5), 1532-1542. https://doi.org/10.55730/1300-0144.5493 https://pubmed.ncbi.nlm.nih.gov/36422497/
33. Akkaya, H., Eyuboglu, S., Erkanlı Senturk, G., & Yilmaz, B. (2017). Investigating the effect of kisspeptin-10 on methionine-induced lipid peroxidation in testicular tissue of young rats. Journal of biochemical and molecular toxicology, 31(5), 10.1002/jbt.21881. https://doi.org/10.1002/jbt.21881 https://pubmed.ncbi.nlm.nih.gov/27900820/
34. Fatima, I., & Qureshi, I. Z. (2022). Intraperitoneal administration of kisspeptin-10 alleviates sodium arsenite-induced reproductive toxicity in adult male mice. Andrology, 54(3), e14347. https://doi.org/10.1111/and.14347 https://pubmed.ncbi.nlm.nih.gov/34897760/
35. Hellier, Vincent; Brock, Olivier; Bakker, Julie . (2019). The role of kisspeptin in sexual behavior. Seminars in Reproductive Medicine, 37(02), 084-092. doi:10.1055/s-0039-3400992 https://pismin.com/10.1055/s-0039-3400992
36. Güvenç, M., & Aksakal, M. (2018). Mitigating effect of kisspeptin-10 on methotrexate-induced sperm damage and testicular oxidative stress in rats. Andrology, 50(8), e13057. https://doi.org/10.1111/and.13057 https://pubmed.ncbi.nlm.nih.gov/29862548/
37. Mattam, U., Talari, N. K., Paripati, A. K., Krishnamoorthy, T. and Sepuri, N. B. V. (2021). Kisspeptin preserves mitochondrial function by inducing mitophagy and autophagy in aging rat brain hippocampus and human neuronal cell line. Biochimica et biophysica acta. Molecular cell research, 1868(1), 118852. https://doi.org/10.1016/j.bbamcr.2020.118852 https://pubmed.ncbi.nlm.nih.gov/32926943/.
38. Kadokawa, H., Matsui, M., Hayashi, K., Matsunaga, N., Kawashima, C., Shimizu, T., Kida, K., & Miyamoto, A. (2008). Periparturient administration of kisspeptin-10 increases plasma GH and LH concentrations in prepubertal Holstein heifers. The Journal of Endocrinology, 196(2), 331-334. https://doi.org/10.1677/JOE-07-0504 https://pubmed.ncbi.nlm.nih.gov/18252956/.
39. Suzuki, S., Kadokawa, H., & Hashizume, T. (2008). Direct kisspeptin-10 stimulation on luteinizing hormone secretion from bovine and porcine anterior pituitary cells. Animal Reproduction Science, 103(3-4), 360-365. https://www.sciencedirect.com/science/article/pii/S0378432007002035.
40. Redmond, J. S., Macedo, G. G., Velez, I. C., Caraty, A., Williams, G. L., & Amstalden, M. (2011). Kisspeptin activates the hypothalamic-adenohypophyseal-gonadal axis in prepubertal ewe lambs. Reproduction (Cambridge, England), 141(4), 541-548. https://doi.org/10.1530/REP-10-0467 https://pubmed.ncbi.nlm.nih.gov/21273366/.