Kisspeptin-10 (KP-10) overview
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Kisspeptin-10 (KP-10) is a short peptide that is part of the larger kisspeptin family of peptides, which are critical regulators of the hypothalamic-pituitary-gonadal (HPG) axis and reproductive function. Kisspeptins are encoded by the KISS1 gene and are involved in the regulation of gonadotropin-releasing hormone (GnRH) secretion, playing a central role in puberty onset and reproductive function. KP-10 is the shortest biologically active form of kisspeptin and retains full receptor activity, making it a valuable tool in research on reproductive endocrinology, cancer biology, and metabolic regulation.
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Molecular Structure and Sequence:
Molecular Formula: C63H83N17O14
Molecular Weight: 1302.46 g/mol
Amino Acid Sequence: Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2 (Y-N-W-N-S-F-G-L-R-F-NH2)
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KP-10 is a decapeptide derived from the carboxyl-terminal region of the kisspeptin precursor protein. It is amidated at the C-terminus, which enhances its stability and bioactivity. Despite being the shortest active form, KP-10 exhibits potent agonist activity at the kisspeptin receptor (KISS1R or GPR54).
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Mechanism of Action:
Kisspeptin-10 exerts its biological effects through high-affinity binding to the KISS1 receptor (KISS1R), a G-protein-coupled receptor (GPCR) also known as GPR54. The mechanism of action involves several key steps:
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1. Receptor Binding:
KP-10 binds to the extracellular domain of the KISS1R receptor, which is primarily expressed in the hypothalamus, pituitary gland, and gonads.
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2. Activation of Intracellular Signaling:
Upon binding, KP-10 induces a conformational change in KISS1R, which activates downstream intracellular signaling pathways, including:
Gq/11 protein activation
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Stimulation of phospholipase C (PLC)
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Increase in inositol trisphosphate (IP3) and diacylglycerol (DAG) levels
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Elevation of intracellular calcium (Ca²⁺) levels
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3. GnRH Secretion:
Increased intracellular calcium levels stimulate the secretion of gonadotropin-releasing hormone (GnRH) from hypothalamic neurons.
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4. Pituitary Gonadotropin Release:
GnRH binds to GnRH receptors in the anterior pituitary, leading to the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which regulate gonadal function, steroidogenesis, and gametogenesis.
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5. Regulation of Reproductive Function:
The downstream effects of KP-10-induced GnRH release include:
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Induction of puberty:
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Regulation of estrous and menstrual cycles
Maintenance of fertility
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Physiological and Research Significance:
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Puberty and Reproductive Health: KP-10 is essential for the onset of puberty and the maintenance of reproductive health.
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Hypogonadotropic Hypogonadism: Mutations in the KISS1 or KISS1R genes have been linked to reproductive disorders such as idiopathic hypogonadotropic hypogonadism (IHH).
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Cancer Research: Kisspeptins have been implicated in cancer metastasis, particularly in melanoma and breast cancer, due to their role in inhibiting cell migration and invasion.
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Metabolism and Energy Homeostasis: KP-10 may also regulate metabolic function and energy balance through its interaction with hypothalamic circuits.
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Pharmacokinetics and Stability:
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KP-10 is rapidly degraded by proteolytic enzymes in circulation, resulting in a short half-life.
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Structural modifications, such as C-terminal amidation, improve its stability and resistance to enzymatic degradation.
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Administration routes in research typically include intravenous (IV) or intracerebroventricular (ICV) injection.
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Potential Research Applications:
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Neuroendocrinology: Investigating the role of kisspeptins in regulating GnRH and reproductive function.
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Oncology: Exploring the anti-metastatic effects of kisspeptins in cancer models.
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Metabolic Studies: Studying the interplay between kisspeptins, appetite regulation, and metabolic pathways.
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Contraception and Fertility Treatments: Developing kisspeptin-based therapies for infertility and reproductive disorders.
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Safety and Toxicology:
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KP-10 has shown no significant toxicity in preclinical models at research doses.
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Potential off-target effects and receptor desensitization may occur at high concentrations.
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Further research is needed to evaluate long-term effects and pharmacological safety.
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**For Research Purposes Only.
**Not for Human Consumption.
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Kisspeptin-10 is intended for laboratory research and investigational use only. It is not approved for human or veterinary use, medical diagnosis, treatment, or therapy. Proper handling and safety precautions should be followed in accordance with institutional guidelines.