Kisspeptin 10

Kisspeptin-10 is a naturally occurring peptide derived from the larger kisspeptin protein, which is encoded by the KISS1 gene. It consists of ten amino acids and is primarily produced in the hypothalamus, where it plays a role in regulating reproductive hormone release.

It is believed to help stimulate the release of gonadotropin-releasing hormone, which can influence fertility and reproductive function. Some studies suggest it may enhance libido and support hormonal balance by modulating key endocrine pathways involved in sexual and reproductive health.

The peptide Kisspeptin-10 (KP-10) has been shown in animal and human studies to strongly stimulate the reproductive hormonal axis. In rodent and human experiments, KP-10 increases secretion of gonadotropins such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and in men it also enhances testosterone release. On a developmental level, KP-10 is critical to the onset of puberty and normal reproductive function across mammals, indicating its role in both maturation and adult fertility ^{1, 2}.

In addition, KP-10 was originally identified as part of the KISS1 gene, which acts as a metastasis suppressor in several cancers by inhibiting tumor cell invasion and spread, suggesting possible relevance to cancer biology. Emerging animal work also suggests that KP-10 may improve testicular redox status and reduce cellular oxidative stress under conditions of thyroid dysfunction, indicating a potential benefit in male reproductive tissue resilience. Some evidence also points toward KP-10 influencing brain processing of sexual and attraction cues in women with hypoactive sexual desire disorder (HSDD), where administration modulated neural responses related to sexual arousal and desire ^{3, 4}. Therefore, KP-10’s main benefits include activation of reproductive hormone release, support for sexual maturation and reproductive function, possible antioxidant effects in reproductive tissues, modulation of sexual desire-related brain pathways, and potential involvement in metastasis suppression.

Research in animals indicates that Kisspeptin‑10 (KP-10) may impair vascular and endothelial health. In cultured human endothelial cells KP-10 reduced tube-formation, triggered cellular senescence (marked by increased p53 and reduced SIRT1) and impaired blood-flow recovery in ischemic rat limbs. In animal models of atherosclerosis (ApoE-/- mice), KP-10 accelerated plaque progression by increasing monocyte adhesion, foam-cell formation, and plaque instability ^{5, 6}.

Additional research in rats found that KP-10 altered myocardial structure, with evidence of mitochondrial damage and increased fibrosis in the heart following peptide administration. In vitro, KP-10 also inhibited the osteogenic differentiation of bone-marrow mesenchymal stromal cells, suggesting possible interference with bone formation processes ^{7, 8}. Overall, the main negative side-effects of Kisspeptin-10 appear to include vascular endothelial dysfunction, atherogenic acceleration, myocardial structural changes, and impaired bone-cell differentiation.

Kisspeptin‑10 binds to its receptor KISS1R (also known as GPR54) on neurons in the hypothalamus, triggering G-protein signalling that leads to release of Gonadotropin‑releasing hormone (GnRH). The GnRH then stimulates the pituitary gland to secrete the gonadotropins Luteinizing hormone (LH) and Follicle‑stimulating hormone (FSH) into the bloodstream. In primate and human studies this sequence of events results in a rise in LH and FSH quickly after kisspeptin-10 exposure, indicating that the peptide acts upstream in the reproductive hormone axis ^{9, 10, 11}. Thus, kisspeptin-10 operates by activating KISS1R receptors on GnRH neurons, initiating a cascade that powerfully drives the hypothalamic-pituitary-gonadal axis.

The FDA lists Kisspeptin-10 among peptide bulk substances that raise safety and characterization concerns for compounding and states it lacks sufficient safety information to support use in humans ¹². For sports, KP-10 as prohibited under current WADA rules and avoid use in sport. Anti-doping authorities have funded methods to detect kisspeptin and its analogues ¹³.