Research Brief
What Is Kisspeptin?
Resposta Rapida
Visao Geral Kisspeptin refers to a family of neuropeptides derivado(a) de the KISS1 gene, originally descoberto(a) em 1996 by Danny R. Welch and J.H. Lee in Hershey, Pennsylvania, como um(a) melanoma metastasis suppressor. The gene was named "KiSS-1" to honor the discovery location near the Hershey'...
Visao Geral
Kisspeptin refers to a family of neuropeptides derivado(a) de the KISS1 gene, originally descoberto(a) em 1996 by Danny R. Welch and J.H. Lee in Hershey, Pennsylvania, como um(a) melanoma metastasis suppressor. The gene was named "KiSS-1" to honor the discovery location near the Hershey's Kisses chocolate factory, with "SS" denoting "suppressor sequence."[1]
The KISS1 gene encodes a 145-aminoacido prepro-kisspeptin precursor que undergoes proteolytic cleavage to produce four biologically ativo(a) isoforms: Kisspeptin-54 (Kp-54), Kp-14, Kp-13, and Kp-10. All isoforms share a conserved C-terminal decapeptide containing an RF-amide motif (Arg-Phe-NH₂) essencial para binding and activating the KISS1R (GPR54) receptor.[2][3]
Kp-54 is o(a) principal circulating form with a meia-vida of ~27.6 minutes; the shorter Kp-10 (~4 min meia-vida) exibe full intrinsic bioactivity e e highly conserved across species.[5]
In 2003, Stephanie Seminara and colleagues made the landmark discovery que loss-of-function mutations in KISS1R (GPR54) cause idiopathic hypogonadotropic hypogonadism and pubertal failure — establishing kisspeptin como o(a) gatekeeper of sexual maturacao.[4]
Kisspeptin is atualmente investigacional — not aprovado(a) por the FDA or EMA for general clinical use. It is prohibited by WADA under S2 (Peptide Hormones, Growth Factors) as it estimula LH/FSH/testosterone production.[7]
Referencias
- Lee JH, Miele ME, Hicks DJ, Phillips KK, Trent JM, Weissman BE, Welch DR. KiSS-1, um(a) novo(a) human malignant melanoma metastasis-suppressor gene. Journal do(a) National Cancer Institute. 1996;88(23):1731-1737.
- Ohtaki T, Shintani Y, Honda S, et al. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature. 2001;411(6837):613-617.
- Kotani M, Detheux M, Vandenbogaerde A, et al. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands do(a) orphan G protein-coupled receptor GPR54. Journal of Biological Chemistry. 2001;276(37):34631-34636.
- Seminara SB, Messager S, Chatzidaki EE, et al. The GPR54 gene como um(a) regulator of puberty. New England Journal of Medicine. 2003;349(17):1614-1627.
- Dhillo WS, Chaudhri OB, Patterson M, et al. Kisspeptin-54 estimula the hypothalamic-pituitary gonadal axis in human males. Journal of Clinical Endocrinology & Metabolism. 2005;90(12):6609-6615.
- Dhillo WS, Chaudhri OB, Thompson EL, et al. Kisspeptin-54 estimula gonadotropin release a maioria potently durante o(a) preovulatory phase do(a) menstrual cycle in women. Journal of Clinical Endocrinology & Metabolism. 2007;92(10):3958-3966.
- World Anti-Doping Agency. The Lista de Substancias Proibidas. S2 Hormonios Peptidicos, Fatores de Crescimento, Substancias Relacionadas e Mimeticos. WADA. Updated 2025.
- de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E. Hypogonadotropic hypogonadism due to loss of function do(a) KiSS1-derived peptide receptor GPR54. Proceedings do(a) National Academy of Sciences. 2003;100(19):10972-10976.
- Abbara A, Eng PC, Phylactou M, et al. Kisspeptin agonista do receptor has potencial terapeutico for female reproductive disorders. Journal of Clinical Investigation. 2020;130(12):6739-6753.
- Abbara A, Jayasena CN, Christopoulos G, et al. Efficacy of kisspeptin-54 to trigger oocyte maturacao in women at alto(a) risk of OHSS during IVF therapy. Journal of Clinical Endocrinology & Metabolism. 2015;100(9):3322-3331.
- Abbara A, Clarke S, Islam R, et al. A second dose of kisspeptin-54 melhora oocyte maturacao in women at alto(a) risk of OHSS: a phase 2 randomizado controlled trial. Human Reproduction. 2017;32(9):1915-1924.
- Jayasena CN, Nijher GM, Chaudhri OB, et al. Subcutaneous injection of kisspeptin-54 acutely estimula gonadotropin secretion in women with hypothalamic amenorrhea, but cronico(a) administration causes tachyphylaxis. Journal of Clinical Endocrinology & Metabolism. 2009;94(11):4315-4323.
- Jayasena CN, Nijher GM, Abbara A, et al. Twice-weekly administration of kisspeptin-54 por 8 semanas estimula release of reproductive hormones in women with hypothalamic amenorrhea. Clinical Pharmacology & Therapeutics. 2010;88(6):840-847.
- MacLean DB, Matsui H, Suri A, Neuwirth R, Colombel M. Sustained exposure para o(a) investigacional kisspeptin analog, TAK-448, down-regula testosterone no(a) castration range in healthy males e em patients with prostate cancer. Journal of Clinical Endocrinology & Metabolism. 2014;99(8):E1445-E1453.
- Skorupskaite K, et al. KP-10 infusion in PCOS women. Human Reproduction. 2020.
- Comninos AN, Wall MB, Demetriou L, et al. Kisspeptin modula sexual and emotional brain processing in humans. Journal of Clinical Investigation. 2017;127(2):709-719.
- Mills EG, et al. HSDD in men — kisspeptin aumenta penile tumescence and sexual brain processing. JAMA Network Open. 2023.
- Izarraras L, et al. Kisspeptin agonist reduz hepatico(a) de novo lipogenesis in MASLD via AMPK-SREBP-1c-CIDEA. 2025.
- Mills EG, et al. Intranasal kisspeptin-54 rapidly estimula gonadotropin release in humans: a non-invasive delivery route. eBioMedicine. 2025.
- Jayasena CN, Abbara A, et al. Kisspeptin-54 desencadeia egg maturacao in women undergoing in vitro fertilization. Journal of Clinical Investigation. 2014;124(8):3667-3677.
- Comninos AN, et al. Acute kisspeptin administration aumenta osteocalcin in healthy men. Journal of Clinical Endocrinology & Metabolism. 2022.
- Izzi-Engbeaya C, et al. Kisspeptin aumenta glucose-estimulou secrecao de insulina in healthy men. Diabetes, Obesity and Metabolism. 2018.
- Seminara SB, et al. Continuous human metastin 45-54 infusion desensitizes GPR54-induziu GnRH release in juvenile male rhesus monkeys. 2006.
- Terse PS, et al. Kisspeptin-10 toxicology studies in dogs — NOAEL at 1000 µg/kg IV × 14 days. 2021.
- Thompson EL, et al. Chronic subcutaneo(a) administration of kisspeptin-54 causes testicular degeneration in adult male rats. 2006.
- Dinh TO, et al. Kisspeptin-13 exacerbates cronico(a) doenca renal and uremic cardiomiopatia in rats. 2023.
- George JT, Veldhuis JD, Roseweir AK, et al. Kisspeptin-10 e um(a) potente stimulator of LH and aumenta pulse frequency in men. Journal of Clinical Endocrinology & Metabolism. 2011;96(8):E1228-E1236.
- Thurston L, et al. Kisspeptin modula brain activity in sexual desire regions in women with HSDD. JAMA Network Open. 2022.
- Nishizawa N, Takatsu Y, et al. Design and synthesis of TAK-448, an investigacional nonapeptide KISS1R agonist. Journal of Medicinal Chemistry. 2016;59(19):8804-8811.
- Chan YM, Butler JP, Pinnell NE, et al. Kisspeptin resets the hypothalamic GnRH clock in men. Journal of Clinical Endocrinology & Metabolism. 2011;96(6):E908-E915.
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Este conteudo e fornecido apenas para fins educacionais e informativos. Os produtos sao fornecidos apenas para estudos in vitro e nao sao medicamentos, drogas ou suplementos. Nao aprovado pela FDA para prevenir, tratar ou curar qualquer condicao.
