Kisspeptin-10

Research

Kisspeptin-10 Peptide Structure

What is Kisspeptin-10?

Kisspeptin-10 (KP-10) represents the shortest biologically active fragment of the kisspeptin family of peptide hormones, which play important roles in reproductive physiology and neuroendocrine function. First identified through the characterization of the KISS1 gene product, KP-10 consists of the C-terminal decapeptide sequence (YNWNSFGLRF-NH2) that is essential for receptor binding and biological activity. This peptide acts as a potent endogenous ligand for the G protein-coupled receptor GPR54 (also known as KISS1R), initiating intracellular signaling cascades that regulate gonadotropin-releasing hormone (GnRH) secretion.

Kisspeptin-10 and Testosterone Levels

Research has revealed complex interactions between kisspeptin-10 and testosterone, with varying effects depending on different factors. Kisspeptin-10 primarily acts by stimulating the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. This leads to increased secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland. LH, in particular, stimulates testosterone production in the testes [R].

Kisspeptin-10’s ability to stimulate the hypothalamic-pituitary-gonadal axis suggests potential applications in treating certain forms of infertility or hypogonadism. Kisspeptin-10 serves as a valuable tool for studying the neuroendocrine regulation of reproduction and testosterone production [R].

KP-10 and Sexual Arousal

Kisspeptin-10 demonstrates a notable ability to boost sexual activity in male rats. Studies have shown that it can:

• Increase copulation rates
• Raise the number of ejaculations before sexual exhaustion
• Reduce rest periods between mating attempts [R].

Kisspeptin-10 appears to have a direct impact on sexual arousal and motivation:

• It promotes high arousal in male rats, particularly in the middle and end stages of courtship cycles [R]
• Intranasal administration of kisspeptin-10 increased sexual motivation in male rats without affecting testosterone levels [R]

In human studies involving men with hypoactive sexual desire disorder (HSDD), kisspeptin administration showed promising results:

• Increased penile tumescence during erotic visual stimuli
• Enhanced sexual brain processing in regions governing sexual responses [R]

Kisspeptin-10 showed more sustained effects on sexual activity throughout the courtship cycle compared to PT-141, which primarily facilitated sexual activity at the onset and middle of the cycle [R]. Unlike some GnRH analogues that increased testosterone without affecting sexual motivation, kisspeptin-10 demonstrated the ability to increase sexual motivation independently of testosterone levels.

The research on kisspeptin-10 points to its potential as a therapeutic target for sexual dysfunction:

• It may offer a novel approach for treating conditions like HSDD, which affects a significant portion of the male population and currently lacks licensed treatment options [R].
• The ability of kisspeptin to influence sexual arousal through both hormonal and non-hormonal pathways makes it a particularly interesting candidate for further investigation

KP-10 and Cancer Research

Studies have shown that KP-10 interacts with the G protein-coupled receptor KISS1R (also known as GPR54), influencing various cellular processes in different cancer types

Research on cervical cancer has yielded promising results. KP-10 analogs have demonstrated the ability to hinder cervical cancer cell proliferation and migration by modulating kinase signaling pathways [R]. These findings suggest potential therapeutic applications for KP-10 analogs in managing cervical cancer progression.

In other cancer types, such as colon, lung, and brain cancer, KP-10 has shown anti-metastatic properties [R].

The antiproliferative effects of KP-10 have been observed to depend on KISS1R expression levels. In cells artificially overexpressing KISS1R, KP-10 significantly inhibited proliferation. However, this effect was not observed in cells with endogenous KISS1R expression, suggesting that the antiproliferative action of KP-10 may be influenced by receptor expression levels [R].

KP-10 and Cardiovascular Health

A 2021 study found that administering kisspeptin-10 regulated mTOR and AKT activities and oxidative stress in mouse cardiac tissue. This could have implications for heart disease treatment, as these pathways are often implicated in cardiovascular disorders [R].

A 2023 study found that kisspeptin-10 increased collagen content in the myocardium, which could alter the structure of myocardial cells and potentially influence heart disease progression [R].

In humans, ischemic heart disease has been associated with a decrease in cardiac kisspeptin levels. This suggests that kisspeptin-10 could play a role in the development or progression of certain types of heart disease [R].

KP-10, Metabolism and Appetite Control

Some studies have shown that kisspeptin-10 can suppress appetite and energy expenditure [R].