Kisspeptin-10

Mechanism (as reported)

A study reported that activation of GPR54 by kisspeptin-10 in osteoclasts leads to up-regulation of Dusp18 and dephosphorylation of Src at Tyr416, affecting osteoclast activity and bone loss. (PMID: 38346942) A review and related chapter material reported that kisspeptin binds KISS1R (GPR54) on GnRH neurons and stimulates GnRH secretion as a gating signal for downstream reproductive events. (PMIDs: 23550006, 30086862) A study reported that kisspeptin-10 increases myocardium/cardiac-fibroblast collagen content in association with focal adhesion kinase (FAK) phosphorylation, and that blocking FAK negated the kisspeptin-10 effect. (PMID: 37968564)

Key findings (each cites a source)

• A review reported that hypothalamic kisspeptin neurons act as a nodal regulatory center for reproductive function, modulating GnRH release, and are tightly regulated by metabolic factors affecting kisspeptin synthesis and release. (PMID: 32427949) [PMID 32427949]
• A chapter/review reported that kisspeptin binds to its cognate receptor KISS1R (GPR54) on GnRH neurons and stimulates their activity, providing an obligatory gating signal for GnRH secretion and downstream reproductive events. (PMID: 23550006) [PMID 23550006]
• A review on central precocious puberty reported that the kisspeptin system plays a key role in early activation of the HPG axis and that mutations in the kisspeptin system, MKRN3, and DLK1 have been identified in sporadic and familial cases of CPP. (PMIDs: 30086862) [PMID 30086862]
• An osteoclast study reported that GPR54 activation by kisspeptin-10 causes Dusp18 to dephosphorylate Src at Tyr416 and that Gpr54 can recruit active Src and the Dusp18 phosphatase to its C-terminal proline/arginine-rich motif, with Kp-10 leading to up-regulation of Dusp18. (PMID: 38346942) [PMID 38346942]
• The same osteoclast study reported that Kiss1, Gpr54, and Dusp18 knockout mice show osteoclast hyperactivation and bone loss, and that kisspeptin-10 abrogated bone loss by suppressing osteoclast activity in vivo. (PMID: 38346942) [PMID 38346942]
• A rat study reported that the antidepressant-like effects of kisspeptin-10 were reversed by the kisspeptin antagonist peptide 234 and that this indicates involvement of GPR54 receptors in mediating these effects. (PMID: 39605118) [PMID 39605118]
• A rat study reported that the kisspeptin-10 antidepressant-like effects involved, at least in part, interactions with alpha-2 adrenergic and 5-HT2 serotonergic receptors, as assessed using yohimbine and cyproheptadine. (PMID: 39605118) [PMID 39605118]
• A cardiac study reported that kisspeptin-10 increases collagen content in the myocardium and that it elevates phosphorylated focal adhesion kinase (FAK) levels in human cardiac fibroblasts; the study further reported that FAK inhibition negated the kisspeptin-10 stimulatory effect on collagen deposition. (PMID: 37968564) [PMID 37968564]
• The same cardiac study reported that kisspeptin-10 increased procollagen propeptides (PICP and PIIICP) in fibroblast culture medium and PIIICP in mouse serum, inhibited release of MMP-1,-2,-9, increased release of TIMP-1,-2,-4, and increased expression of α1 chains of procollagen type I and III in vitro; it also reported the profibrotic activity was mediated by FAK and not dependent on TGF-β1. (PMID: 37968564) [PMID 37968564]
• A urine LC-HRMS method study reported validation of screening and confirmation procedures for kisspeptin-10 in urine, including incubation in human serum to mimic endogenous metabolism and identification of metabolites corresponding to peptide fragments y9, y8, y7, and y5. (PMID: 38978171) [PMID 38978171]
• The urine LC-HRMS study reported detection of a degradation product probably caused by oxidation of a tryptophan residue into a kynurenine residue and noted that further work should elucidate kinetic parameters to improve product stability. (PMID: 38978171) [PMID 38978171]
• The urine LC-HRMS study reported analysis of a black-market vial of kisspeptin-10, stating it contained no unexpected impurities but appeared to have undergone more degradation than the purchased reference standard. (PMID: 38978171) [PMID 38978171]