Kisspeptin-10 — 5mg

Kisspeptin-10 is a synthetic decapeptide that represents the shortest, fully active C-terminal fragment of the native kisspeptin protein (Kiss1). Its amino acid sequence is Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2 (YNWNSFGLRF-NH2), classifying it as a member of the RF-amide peptide family due to its characteristic C-terminal arginine-phenylalanine-amide motif. This structural feature is critical for its biological activity. Kisspeptin-10 is renowned in the scientific community as the primary endogenous agonist for the G protein-coupled receptor 54 (GPR54), now more formally known as KISS1R. The discovery of the Kiss1 gene and its peptide products revolutionized the field of neuroendocrinology, revealing a master regulator of the reproductive axis.

The significance of Kisspeptin-10 in laboratory research stems from its potent and specific action on hypothalamic neurons that express KISS1R. These neurons are primarily responsible for secreting gonadotropin-releasing hormone (GnRH), the principal hormone that governs the entire hypothalamic-pituitary-gonadal (HPG) axis. By potently stimulating GnRH release, Kisspeptin-10 acts as a critical upstream regulator of puberty onset, ovulation, and the maintenance of normal reproductive function in various preclinical models. Its well-defined structure and mechanism make it an invaluable molecular tool for investigators studying the complex interplay between neural signaling and endocrine regulation.

Originally, the KISS1 gene was identified for its role as a metastasis suppressor in melanoma cell lines, highlighting a separate avenue of research interest in oncology. However, its profound effects on the HPG axis have since become the dominant focus of investigation. Researchers utilize Kisspeptin-10 in a wide array of experimental settings, from in vitro cell culture assays to in vivo animal models, to dissect the molecular pathways controlling fertility, explore potential links between metabolism and reproduction, and investigate the mechanisms of cancer metastasis. As a research-grade compound, Kisspeptin-10 provides a reliable and consistent tool for probing these fundamental biological processes.

For Research Use Only. This product is not intended for human consumption or for use in any diagnostic or therapeutic procedures.

The mechanism of action of Kisspeptin-10 is mediated primarily through its high-affinity binding to and activation of the KISS1 receptor (KISS1R), formerly known as G protein-coupled receptor 54 (GPR54). KISS1R is predominantly expressed on the surface of gonadotropin-releasing hormone (GnRH) neurons located within specific regions of the hypothalamus, including the arcuate nucleus (ARC) and the anteroventral periventricular nucleus (AVPV). Upon binding, Kisspeptin-10 induces a conformational change in the KISS1R, initiating a canonical Gαq/11 signal transduction cascade, which is the cornerstone of its physiological effect on the reproductive axis.

Activation of the Gαq/11 subunit triggers the downstream enzyme phospholipase C (PLC). PLC, in turn, catalyzes the hydrolysis of the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) into two crucial second messengers: inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 diffuses through the cytoplasm and binds to IP3 receptors on the endoplasmic reticulum, prompting the rapid release of stored intracellular calcium (Ca2+) into the cytosol. Concurrently, DAG remains in the plasma membrane and, along with the elevated cytosolic Ca2+, activates various isoforms of protein kinase C (PKC).

The synergistic action of increased intracellular Ca2+ and PKC activation leads to a profound depolarization of the GnRH neuron's cell membrane. This is achieved through the modulation of ion channel activity, including the opening of transient receptor potential canonical (TRPC) channels and the closure of inwardly rectifying potassium (Kir) channels. The resulting increase in neuronal excitability triggers a burst of action potentials, culminating in the pulsatile secretion of GnRH from the neuron terminals into the hypophyseal portal circulation. This precise, pulse-driven release is critical for proper downstream signaling.

Once released, GnRH travels to the anterior pituitary gland, where it binds to its own receptor on gonadotroph cells. This interaction stimulates the synthesis and co-secretion of two essential gonadotropins: luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones enter the systemic circulation and act on the gonads (testes and ovaries) to regulate gametogenesis and steroidogenesis. Beyond this primary pathway, research in other cell types, such as cancer cell lines, has suggested that KISS1R activation can also engage other signaling pathways, including the mitogen-activated protein kinase (MAPK/ERK) pathway, which may underlie its observed anti-metastatic properties in experimental models. The study of Kisspeptin-10 provides a powerful means to investigate these intricate signaling networks in controlled laboratory environments.

Kisspeptin-10 is a pivotal tool in a range of advanced research applications, primarily centered on neuroendocrinology, reproductive biology, and oncology. Its most prominent use is in studies investigating the regulation of the hypothalamic-pituitary-gonadal (HPG) axis. Researchers employ Kisspeptin-10 in both in vivo animal models (e.g., rodents, sheep, non-human primates) and in vitro hypothalamic explant cultures to elucidate its role as the master regulator of gonadotropin-releasing hormone (GnRH) secretion. These studies aim to understand the fundamental mechanisms governing puberty onset, the neuroendocrine control of ovulation and the menstrual/estrous cycle, and the feedback loops involving gonadal steroids.

In the field of reproductive science, Kisspeptin-10 is used to model and investigate conditions of HPG axis dysfunction. For instance, preclinical studies utilize Kisspeptin-10 to explore its effects in animal models of hypogonadotropic hypogonadism, polycystic ovary syndrome (PCOS), and stress-induced reproductive suppression. By administering Kisspeptin-10 in controlled laboratory settings, researchers can assess its capacity to modulate GnRH pulse frequency and amplitude, thereby restoring downstream gonadotropin secretion and gonadal function in these models. This allows for a detailed examination of the kisspeptin system's role in both physiological and pathophysiological states.

Another significant area of research is the intersection of metabolism and reproduction. The kisspeptin system is believed to be a key conduit through which metabolic cues, such as leptin and insulin signaling, influence reproductive capability. Laboratory investigations use Kisspeptin-10 to probe how nutritional status and energy balance impact GnRH neuronal activity. These studies in animal models are critical for understanding how metabolic disorders can lead to reproductive deficits and for mapping the neural circuits that integrate these two essential physiological systems.

Beyond endocrinology, Kisspeptin-10 is studied in oncology research due to the original discovery of its parent gene, KISS1, as a metastasis suppressor. In vitro studies using various cancer cell lines (e.g., melanoma, breast, and pancreatic cancer) investigate the ability of Kisspeptin-10 to inhibit cell migration, invasion, and adhesion through the KISS1R. These cellular and molecular biology studies aim to dissect the signaling pathways, such as the suppression of matrix metalloproteinases or modulation of the focal adhesion kinase (FAK) pathway, that contribute to these anti-metastatic effects. Such research provides valuable insights into the fundamental processes of cancer progression.