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Hedi Raizer

Journal 7 min read

What is Kisspeptin-10?

Kisspeptin-10 is a decapeptide fragment of the KISS1 gene product and a potent agonist of the KISS1R receptor. This article summarises the research on its pharmacology, from gonadotropin secretion in men to metabolic and

peptides-pro Editorial

Kisspeptin-10 (KP-10) is a decapeptide that corresponds to the C-terminal bioactive core of the kisspeptin family of neuropeptides, which are encoded by the KISS1 gene. It is also known as metastin 45–54, and its sequence is Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2, with a molecular formula of C63H83N17O14 and a molecular weight of approximately 1302.5 Da. The peptide is amidated at its C-terminus, a modification that is important for its activity. Kisspeptin-10 is the shortest naturally occurring kisspeptin fragment that retains full agonist activity at the KISS1 receptor (KISS1R, also known as GPR54), a G protein-coupled receptor that signals primarily through Gq/11 to activate phospholipase C and downstream calcium and ERK pathways.

The KISS1/KISS1R axis is best known for its role in the neuroendocrine control of reproduction, where kisspeptin signalling in the hypothalamus stimulates gonadotropin-releasing hormone (GnRH) release and, consequently, gonadotropin secretion. Research on kisspeptin-10 spans reproductive endocrinology, metabolism, placental biology, and cancer cell models, and the sections below summarise key findings from the available evidence.

Research Studies

Kisspeptin-10 and gonadotropin secretion in healthy men

In a randomized, single-blinded, placebo-controlled study, 15 healthy men were recruited to evaluate acute and chronic subcutaneous administration of kisspeptin-10. The study characterised the acute dose–response relationship to subcutaneous kisspeptin-10 infusion, assessed the effects of continuous infusion over 5 days, and examined daily intermittent administration (8 hours on, 16 hours off) for 12 days. The authors reported that chronic subcutaneous kisspeptin-10 stimulated gonadotropin secretion for 12 days in healthy men [1].

Kisspeptin-10 and dynamic LH secretion during continuous infusion in men

A separate study examined the effects of continuous kisspeptin administration on luteinizing hormone (LH) secretion in healthy men. Three healthy adult men received a continuous intravenous infusion of kisspeptin-10 at a dose of 12.5 mcg/kg/h for 24 hours and underwent frequent blood sampling to characterise the effect on reproductive hormones. The objective was to determine whether continuous kisspeptin administration dampens kisspeptin-induced GnRH release, as had been observed in non-human primates but not replicated in limited human studies. The findings provided data on the dynamic modulation of LH secretion by continuous kisspeptin infusion in this small cohort [6].

Kisspeptin-10 and the KISS1/KISS1R axis in human placentation

The KISS1/KISS1R axis has been studied in the context of human placentation, with implications for foetal growth restriction (FGR) and pre-eclampsia. A review of molecular mechanisms noted that pre-eclampsia and FGR are major pregnancy complications driven primarily by placental dysfunction, and that kisspeptin signalling is directly associated with trophoblast signalling pathways. The review suggested that biomarkers linked to trophoblast signalling, including kisspeptin, have the potential to improve early risk stratification and enable mechanistic classifications [7].

Kisspeptin-10 and placental mTOR signalling in hypothyroid rats

In a rat model of maternal hypothyroidism, kisspeptin-10 treatment was evaluated for its effects on maternal energy homeostasis and placental expression of mTOR and glucose metabolism mediators. Maternal hypothyroidism was induced by propylthiouracil administration, and kisspeptin-10 treatment began on gestational day 8. The study aimed to assess whether kisspeptin-10 could restore placental mTOR signalling and improve glucose homeostasis mediators disrupted by maternal hypothyroidism. The results indicated that kisspeptin-10 treatment improved feto-placental development in hypothyroid rats [8]. This evidence is animal-only.

Kisspeptin-10 and glycosaminoglycan and decorin content in human cardiac fibroblasts

An in vitro study investigated the influence of kisspeptin-10 on glycosaminoglycan and decorin content in human cardiac fibroblast cultures. Cardiac fibroblasts play a key role in extracellular matrix (ECM) remodelling through the synthesis of glycosaminoglycans and proteoglycans such as decorin. The study assessed the effects of kisspeptin-10 on these components, with or without signalling inhibitors, and identified a mechanism by which kisspeptin-10 regulates glycosaminoglycan and decorin content in this cell model [3]. This evidence is in vitro.

Kisspeptin-10 and obesity-diabetes in high-fat fed female mice

In a mouse model of diet-induced obesity and diabetes, the effects of twice-daily intraperitoneal administration of kisspeptin-10 (25 nmol/kg) for 21 days were examined in high-fat diet (HFD) fed female mice, with normal diet (ND) mice as an additional control group. Kisspeptin-10 decreased body weight, blood glucose, and energy intake to ND levels. HFD increased circulating follicle-stimulating hormone (FSH) levels, which were further modulated by kisspeptin-10. The study also reported diverse effects on ileal enteroendocrine cells and pancreatic islet morphology [5]. This evidence is animal-only.

Kisspeptin-10 and neurokinin B and dynorphin A in pubertal ewes

A study in ewe lambs investigated the relationship between kisspeptin-10, neurokinin B (NKB), and dynorphin A (Dyn A) during normal and delayed puberty. Twenty-four ewe lambs from single and twin pregnancies were divided into groups, and plasma concentrations of these neuropeptides were measured in relation to the first ovulation time. The aim was to determine changes in kisspeptin-10, NKB, and Dyn A concentrations during puberty and to examine the relationships between these neuropeptides [4]. This evidence is animal-only.

Kisspeptin-10 and the kisspeptin analog C6 in vitro

A comparative in vitro study characterised the pharmacological profiles of human kisspeptin-10 (hKp10), human kisspeptin-54 (hKp54), and the synthetic agonist C6 using HEK293 cells. The study sought to directly compare the effects of these molecules, as direct comparative data were limited. The authors reported that the kisspeptin analog C6 elicited greater tachyphylaxis and transcriptional activation than kisspeptin-10 and kisspeptin-54 [2]. This evidence is in vitro.

Kisspeptin-10 and structural selectivity for KISS1R

Computational studies have explored the structural basis for kisspeptin-10 selectivity toward KISS1R. Kisspeptin-10, as the bioactive core fragment of kisspeptin neuropeptides, has been noted to modulate reward-related behaviours beyond its canonical role in reproductive neuroendocrinology. Behavioural studies in rodent models indicate that kisspeptin-10 promotes impulsive and compulsive-like phenotypes, and computational insights have been used to investigate its selectivity for KISS1R [9]. This evidence includes computational and animal data.

Kisspeptin-10 and the kisspeptin-10/basal LH ratio in precocious puberty

Clinical research has examined the kisspeptin-10/basal LH ratio as a potential tool to improve the differentiation of central precocious puberty (CPP) from premature thelarche (PT). Distinguishing idiopathic central precocious puberty from premature thelarche remains a clinical challenge and often necessitates GnRH stimulation testing. Kisspeptin-10, neurokinin B, and neuropeptide Y are key regulators of GnRH secretion and may serve as surrogate biomarkers. The study reported that the kisspeptin-10/basal LH ratio improved differentiation of these conditions [10]. This evidence is from a clinical study.

Kisspeptin-10 and ovarian cancer progression in vitro

An in vitro and computational study explored the influence of exogenous kisspeptin-10 on the SP1-ZEB1-hTERT pathway in SKOV-3 ovarian cancer cell lines. Ovarian cancer is known for high metastatic ability and telomerase reactivation. The study aimed to investigate whether kisspeptin-10 inhibits ovarian cancer progression through targeting this regulatory axis [11]. This evidence is in vitro and computational.

Kisspeptin-10 and ovarian follicle development in mice

In mice, a study aimed to elucidate how kisspeptin-10 modulates hormone secretion, proliferation, and autophagy of ovarian follicles by regulating associated genes and proteins in vivo and in vitro. Follicular granulosa cells were cultured in EMDM/F12 medium, and the study reported that kisspeptin-10 promotes hormone secretion, ovarian follicle development, and fecundity via the PI3K/AKT/ERK signalling pathway [12]. This evidence is animal and in vitro.

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