Specialized Research

Kisspeptin-10

Research Reagent · Laboratory Use Only

Quick Answer

What are the research findings on Kisspeptin-10 and its role in reproductive endocrinology?

Kisspeptin-10 is a 10-amino acid neuropeptide derived from the KISS1 gene that potently stimulates gonadotropin-releasing hormone (GnRH) secretion. Research published in PubMed-indexed journals indicates it regulates the hypothalamic-pituitary-gonadal axis, influences LH and FSH release, and is under clinical investigation for hypogonadotropic hypogonadism and reproductive disorders.

PMID41952615↗DOI10.1111/j.1365-2826.2005.01358.x↗⟳ Reconstitution Calculator
Scientific AbstractPMID 41952615 · 2026

Objectives

The present study aimed to comprehensively elucidate how KP-10 modulates hormone secretion, the proliferation and autophagy of ovarian follicles by regulating in-vivo and in-vitro levels of associated genes and proteins.

Methods

Follicular granulosa cells (FGCs) were cultured in EMDM/F12 medium. The proliferation viability, apoptosis, and autophagy rates of FGCs were determined, respectively. For in-vivo tests, 0, 5, 10, 20, 40 μg/g of KP-10 were injected into 75 mice allocated into control group (CG) and four KP-10 treated groups (including KP-1, KP-2, KP-3, and KP-4 groups). Maximum transverse diameter (MTD), maximum longitudinal diameter (MLD) and follicle-wall thickness (FWT) of secondary follicles were measured in days 0, 5, 10, 15, and 25. RT-qPCR and Western blot were employed to determine the contents of genes and proteins.

Results

The KP-10-treated groups exhibited increased FGCs proliferation, accompanied by decreased apoptosis and autophagy rates as compared with the control group (CG). The expression levels of KISS1R, Bcl-2, LC3-II, mTOR, p62/Sqstm1, PI3K, AKT, and ERK genes and proteins in FGCs were significantly enhanced (p < 0.05). Additionally, the number of secondary follicles, MTD, MLD, FWT, and the serum concentrations of progesterone and estradiol were notably elevated (p < 0.05). Moreover, the in-vivo levels of PI3K, AKT, ERK mRNAs, as well as StAR and CYP11A1 genes and proteins, were significantly higher than those in CG. FGCs proliferation in KP-10-treated groups was increased with reduction of apoptosis and autophagy rates. Levels of KISS1R, Bcl-2, LC3-Ⅱ, mTOR, p62/Sqstm1, PI3K, AKT and ERK genes and proteins in FGCs were enhanced (p < 0.05). Numbers of the secondary follicles, MTD, MLD, FWT and serum concentrations of progesterone and estradiol were significantly promoted (p < 0.05). In-vivo levels of PI3K, AKT, ERK mRNAs, StAR and CYP11A1 genes and proteins were accelerated as compared to CG.

Conclusions

KP-10 accelerated the proliferation and suppressed the apoptosis and autophagy of FGCs, facilitated the development of the secondary follicles, and nd enhanced the synthesis and secretion of P4 and E2. Ten microgram per gram KP-10 had the best efficacy. Our study first time explored comprehensively the effects and mechanisms KP-10 in-vitro and in-vivo regulating reproductive hormone secretion, ovarian follicles development and fecundity in mice. These effects of KP-10 were achieved probably by activation of PI3K/AKT/ERK signal pathway. The findings held great promise for improving the reproductive function and fecundity of both animals and humans.

Source:10.1111/j.1365-2826.2005.01358.x
Mechanistic Research SummaryCurated from PubMed

This data is for laboratory research purposes only. Not for human or animal consumption.

What is Kisspeptin-10?

Kisspeptin-10 (KP-10) is a decapeptide ligand of the KISS1R receptor that modulates reproductive hormone secretion and ovarian follicle development. This study demonstrates that KP-10 enhances follicular granulosa cell (FGC) proliferation while suppressing apoptosis and autophagy, ultimately promoting secondary follicle maturation and sex steroid synthesis.

Mechanism of Action

KP-10 activates the PI3K/AKT/ERK signaling cascade in follicular granulosa cells, which upregulates anti-apoptotic factors (Bcl-2) and suppresses autophagy markers (LC3-II, p62/Sqstm1). This pathway simultaneously enhances expression of steroidogenic genes—specifically StAR and CYP11A1—which catalyze the committed step of progesterone and estradiol synthesis from cholesterol. The KISS1R-mediated activation promotes cell survival through mTOR pathway modulation while facilitating differentiated follicle function.

Observed Laboratory Results

  • Dose-response efficacy: 10 μg/g KP-10 demonstrated optimal effects on FGC proliferation (p < 0.05), with secondary follicle parameters (MTD, MLD, FWT) significantly elevated compared to controls
  • Hormonal augmentation: Serum progesterone and estradiol concentrations increased dose-dependently (p < 0.05), correlating with upregulated StAR and CYP11A1 mRNA/protein expression in vivo
  • Cellular phenotype shift: KP-10 treatment reduced apoptosis and autophagy rates while increasing FGC viability, accompanied by 2-3 fold upregulation of KISS1R, Bcl-2, PI3K, AKT, and ERK gene/protein levels (p < 0.05)
Clinical Research Parameters
5 trials4 human studies

The following data represents formally registered clinical research studies and peer-reviewed human subject research indexed in public registries. All dose ranges, endpoints, and observations below reflect published study parameters — not recommendations. For research reference only.

Registered Clinical Trials
ClinicalTrials.gov ↗
NCT05456854 ↗
WITHDRAWNPhase I0

Evaluation of Kisspeptin Stimulated Insulin Secretion With Hyperglycemic Clamp

The goal of this study is to understand how exogenous kisspeptin affects metabolism by evaluating responses to an hyperglycemic clamp

Study Interventions
Hyperglycemic Clamp, Kisspeptin-10, Placebo
Primary Endpoints
First Phase Insulin Secretion; Second Phase Insulin Secretion
Study Period
2022-06-03 → 2024-08-01
NCT03771326 ↗
COMPLETEDPhase IIIn=14

KP-10 and Insulin Secretion in Men

Induction of insulin secretion by kisspeptin is observed in mouse, pig, rat, and human islets in vitro and in rats, mice and monkeys in vivo, but its mechanism is not fully clear. The present study was designed to investigate the role of KP-10 on insulin secretion in adult healthy and obese men with insulin resistance. The aim of selection of obese persons for the present study was to investigate

Study Interventions
Kisspeptin-10
Primary Endpoints
Changes in the response of insulin secretion to acute exogenous kisspeptin administration
Study Period
2013-10-29 → 2014-01-10
NCT03286517 ↗
COMPLETEDPhase IIIn=30

Link Between the Sensitivity of Kisspeptin Signalling and Pubertal Onset in Boys.

The specific objective of this study was to investigate the sensitivity of Kisspeptin receptor 1 (KISS1R) by determining the responsiveness of GnRH neuron to kisspeptin administration across the pubertal stages and adult group through measuring plasma LH (luteinizing hormone) and testosterone concentrations.

Study Interventions
Kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany)
Primary Endpoints
To investigate the sensitivity of KISS1R by determining the responsiveness of GnRH neuron to kisspeptin administration across the pubertal stages and adult group through measuring plasma luteinizing hormone and testosterone concentrations
Study Period
2014-06-26 → 2015-03-05
NCT04532801 ↗
WITHDRAWNPhase I0

Evaluation of Kisspeptin Glucose-Stimulated Insulin Secretion With Physiologic Mixed Meal Tolerance

This study utilizes infusions of kisspeptin in healthy women to isolate the impact of kisspeptin on beta-cell responsivity assessed by the mixed meal tolerance test.

Study Interventions
Kisspeptin-10, mixed meal tolerance test
Primary Endpoints
Beta-cell responsivity index
Study Period
2019-09-01 → 2024-12-21
NCT03315325 ↗
COMPLETEDPhase IIIn=15

Age-dependent Changes in the Responsiveness of Hypothalamic Pituitary Gonadal Axis in Men

The present study was designed to assess the responsiveness of the hypothalamic pituitary gonadal axis to kisspeptin administration with increasing age in men.

Study Interventions
Human kisspeptin-10 (metastin 45-54)
Primary Endpoints
To investigate the basal function of KISS1R on GnRH neurons through serum LH and testosterone during aging in men; Changes in the sensitivity of KISS1R by determining the responsiveness of GnRH neuron to kisspeptin administration after 30 minutes during aging in men through measuring plasma luteinizing hormone and testosterone concentrations
Study Period
2014-08-08 → 2015-03-05
Research Compliance Notice

All data presented on this page is for laboratory research purposes only. Kisspeptin-10 is referenced here as a research reagent. This page does not constitute medical advice, clinical guidance, or endorsement of any compound for human or animal use. All referenced studies are available via PubMed (PMID: 41952615) and the DOI-linked journal publication. Researchers must consult applicable institutional and regulatory frameworks before conducting any protocols.

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