Kisspeptin expression in the brain: Catalyst for the initiation of puberty

Abstract

In 2003, two independent groups of researchers discovered almost simultaneously that inactivating mutations of the G protein coupled receptor, GPR54, cause hypogonadotropic hypogonadism in mice and men. Since this discovery, kisspeptins, the natural ligands for GPR54, have been thrust into the reproductive neuroendocrine spotlight, as major regulators of GnRH function. Kisspeptins are the peptide products of the KiSS-1 gene, and potently stimulate gonadotrophin secretion when administered either centrally or peripherally. Expression of KiSS-1 has been localised to specific regions of the hypothalamus in many species and is regulated by gonadal steroids and across the estrous cycle. It appears that kisspeptin transmits steroid feedback signals to GnRH cells, especially the positive feedback effect of estrogen that causes the preovulatory GnRH/LH surge. Importantly, kisspeptin function appears to be fundamental to the initiation of puberty.

Cerebral white matter in early puberty is associated with luteinizing hormone concentrations

“…Recent studies point to the importance of the KiSS1-gene in the initiation of puberty. More specifically, a peptide-product of the KiSS1-gene, kisspeptine, is expressed throughout the brain (for review see Smith and Clarke, 2007). During puberty, mRNA expression of the KiSS1-gene was reported to be upregulated in the hypothalamus (Navarro et al, 2004).…”

Melatonin Controls Seasonal Breeding by a Network of Hypothalamic Targets

“…This is one of the most important findings since the isolation of GnRH more than 30 years ago [41,42,43,44]. In addition, an increasing number of genes is being identified in the hypothalamus of mammals as regulated by photoperiod through the action of melatonin.…”

“…In a variety of models, central and peripheral administrations of Kps potently elicit LH/FSH secretion [42, 43] so that Kps are now considered as the most potent secretagogues of the HPG axis. In rats, central administration of doses as low as 100 fmol to 1 pmol are sufficient to evoke maximal LH secretion [42, 43, 89, 90]. There is evidence to suggest that Kps activate GnRH neurons directly.…”

Peripheral administration of kisspeptin-10 increases plasma concentrations of GH as well as LH in prepubertal Holstein heifers

“…In particular, kisspeptin expressed in GnRH neurons in the arcuate nucleus (ARC) of the mediobasal hypothalamus may be a pivotal regulator of puberty in primates and laboratory animals (Smith & Clarke 2007). Central kisspeptin administration leads to a marked increase of luteinizing hormone (LH) in rodents, primates, and sheep (Gottsch et al 2006), probably by stimulating GnRH secretion from GnRH neurons into portal blood (Plant 2006).…”