What Is the Kisspeptin Peptide and What Does It Do?

Kisspeptin is a peptide hormone that plays a part in regulating the human reproductive system. Its role in fertility and puberty was uncovered after its initial discovery in 1996. The peptide is produced from the KISS1 gene and functions as a neuropeptide, meaning it is made by neurons and acts on other neurons to modulate their activity.

The Reproductive Regulatory Role of Kisspeptin

The primary function of kisspeptin is to manage reproduction by activating the hypothalamic-pituitary-gonadal (HPG) axis. Neurons in the hypothalamus produce kisspeptin, which then acts on neurons responsible for producing Gonadotropin-Releasing Hormone (GnRH). The binding of kisspeptin to its receptor, GPR54 (or KISS1R), on these GnRH neurons triggers the release of GnRH.

This release of GnRH is the foundational step that initiates a hormonal cascade. GnRH travels from the hypothalamus to the pituitary gland, signaling it to secrete two hormones: luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones then travel through the bloodstream to the gonads (the ovaries in females and testes in males), where they stimulate the production of sex hormones like estrogen and testosterone and support the development of eggs and sperm.

One of kisspeptin’s roles is initiating puberty. Before puberty, the HPG axis is relatively dormant. The process begins when kisspeptin neurons increase their signaling, activating the GnRH neurons and setting the reproductive axis in motion.

In adulthood, kisspeptin continues to regulate reproductive functions. In females, it helps control the menstrual cycle and ovulation. In males, it is involved in spermatogenesis and maintaining testosterone levels. Sex hormones from the gonads feed back to the brain to modulate kisspeptin release, creating a regulatory loop.

Kisspeptin’s Influence Beyond Reproduction

Kisspeptin’s functions extend beyond reproduction. The peptide was first discovered for its ability to suppress the spread of melanoma and was originally named metastin. It appears to halt the movement of cancerous cells by activating its receptor on them, which triggers pathways that limit cell motility.

Kisspeptin is also connected to the regulation of mood and emotional behaviors. Its receptors are found in brain areas that process emotions, suggesting it may influence anxiety and stress responses. Fluctuations in kisspeptin signaling might contribute to mood changes linked to hormonal cycles.

Kisspeptin helps integrate the body’s energy status with the reproductive system. Its neurons have receptors for leptin, a hormone signaling energy availability from fat stores. This connection acts as a bridge, ensuring the body has enough metabolic resources for reproduction and helps explain why malnutrition or extreme physical stress can disrupt fertility.

Consequences of Kisspeptin Imbalance

When the body does not produce enough kisspeptin or when its receptor, KISS1R, is non-functional due to genetic mutations, the activation of the HPG axis fails. This results in a condition called idiopathic hypogonadotropic hypogonadism (iHH), characterized by absent or severely delayed puberty and subsequent infertility.

Conversely, excessive kisspeptin signaling can lead to central precocious puberty, where puberty begins at an unusually early age. The premature activation of GnRH neurons accelerates the maturation process, which can have physical and psychosocial consequences for children.

Dysregulated kisspeptin levels are also implicated in other reproductive disorders like Polycystic Ovary Syndrome (PCOS) and hypothalamic amenorrhea. In these conditions, an imbalance in the peptide’s pulsatile release disrupts the timing required for a normal menstrual cycle.

Medical Applications and Ongoing Research

Administering a dose of kisspeptin can serve as a test to assess the functionality of the HPG axis. By measuring the resulting hormone response, clinicians can determine whether a reproductive disorder originates from the hypothalamus and pituitary or from the gonads themselves.

Drugs that mimic or block kisspeptin are being developed for treatment. Kisspeptin agonists, which activate the receptor, show promise for treating delayed puberty or some forms of infertility. They could also be used to induce ovulation in fertility treatments.

Kisspeptin antagonists, which block the receptor, could manage conditions driven by excessive hormone production. This includes treatments for precocious puberty or hormone-sensitive cancers like prostate and breast cancer, where reducing sex hormone levels is a therapeutic goal.