Regulation of the neuroendocrine reproductive axis by kisspeptin-GPR54 signaling

Abstract

The Kiss1 gene codes for a family of peptides that act as endogenous ligands for the G protein-coupled receptor GPR54. Spontaneous mutations or targeted deletions of GPR54 in man and mice produce hypogonadotropic hypogonadism and infertility. Centrally administered kisspeptins stimulate gonadotropin secretion by acting directly on GnRH neurons. Sex steroids regulate the expression of KiSS-1 mRNA in the brain through direct action on KiSS-1 neurons. In the arcuate nucleus (Arc), sex steroids inhibit the expression of KiSS-1, suggesting that these neurons serve as a conduit for the negative feedback regulation of gonadotropin secretion. In the anteroventral periventricular nucleus (AVPV), sex steroids induce the expression of KiSS-1, implying that KiSS-1 neurons in this region may have a role in the preovulatory LH surge (in the female) or sexual behavior (in the male).

Kisspeptins (KiSS-1): Essential Players in Suppressing Tumor Metastasis

“…In humans, this ligand derives from precursor peptide of 145 amino acids in length, with a putative 19 amino acids signal sequence, two potential dibasic cleavage sites, and one putative site for terminal cleavage and amidation. The precursor generates different peptides by photolytic cleavage; thus KPs (also called metastin), is the major peptide that are found to be unstable and may be proteolytically cleaved into the shorter products such as KP-10, KP-13, KP-14 and KP-54 (Smith et al, 2006;Makri et al, 2008).…”

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

“…This relatively newly discovered neuropeptide system has been the subject of considerable attention in the past few years, as the ligand KiSS-1 and its receptor GPR54, are obligatory for the control of GnRH function (reviewed in [147,139]). Significant research shows that expression of KiSS-1 and GPR54 are sexually dimorphic, with most studies focusing on the AVPV as a key control center of the preovulatory GnRH/LH surge, and the arcuate nucleus as a potential target for negative feedback of the hypothalamic-pituitarygonadal axis by steroid hormones [147].…”

“…This relatively newly discovered neuropeptide system has been the subject of considerable attention in the past few years, as the ligand KiSS-1 and its receptor GPR54, are obligatory for the control of GnRH function (reviewed in [147,139]). Significant research shows that expression of KiSS-1 and GPR54 are sexually dimorphic, with most studies focusing on the AVPV as a key control center of the preovulatory GnRH/LH surge, and the arcuate nucleus as a potential target for negative feedback of the hypothalamic-pituitarygonadal axis by steroid hormones [147]. In the context of neural imprinting, when newborn male pups were given a single injection of estradiol on day 1, and hypothalamic gene expression was measured in adulthood at day 60, there was a significant decrease in KiSS-1 mRNA and serum LH, although GnRH and GPR54 mRNA did not differ from controls [105].…”

Kisspeptin neurons mediate reflex ovulation in the musk shrew ( Suncus murinus )

“…Accumulating evidence suggests that in many mammalian species the kisspeptin-GPR54 system plays a critical role in inducing gonadotropin secretion through stimulation of GnRH release (11)(12)(13)(14)(15)(16)(17). Kisspeptin neurons play a role in the generation of the surge mode of GnRH/LH release to mediate the estrogenpositive feedback effect and then ovulation (18)(19)(20)(21) as well as the pulsatile GnRH/LH release responsible for follicular maturation (22,23). Thus, kisspeptin may mediate mating-induced ovulation through GnRH/LH release in the musk shrew.…”