kiss1-protein--human and Gonadal-Disorders

Puberty marks the end of childhood and is a period when individuals undergo physiological and psychological changes to achieve sexual maturation and fertility. The hypothalamic-pituitary-gonadal axis controls puberty and reproduction and is tightly regulated by a complex network of excitatory and inhibitory factors. This axis is active in the embryonic and early postnatal stages of life and is subsequently restrained during childhood, and its reactivation culminates in puberty initiation. The mechanisms underlying this reactivation are not completely known. The age of puberty onset varies between individuals and the timing of puberty initiation is associated with several health outcomes in adult life. In this Series paper, we discuss pubertal markers, epidemiological trends of puberty initiation over time, and the mechanisms whereby genetic, metabolic, and other factors control secretion of gonadotropin-releasing hormone to determine initiation of puberty.

Topics: Adolescent; Child; Female; Gonadal Disorders; Gonadotropin-Releasing Hormone; Humans; Hypothalamo-Hypophyseal System; Kisspeptins; Male; Pituitary-Adrenal System; Puberty; Ribonucleoproteins; RNA-Binding Proteins; Sexual Maturation; Tachykinins; Ubiquitin-Protein Ligases

Kisspeptins, the peptide products of the KiSS-1 gene, bind to the G protein coupled receptor 54 (GPR54). Since 2003, research has revealed the important role of kisspeptins in initiating puberty, timing puberty and regulating fertility in adulthood. Specific mutations in GPR54 gene cause either delayed/absent puberty or precocious puberty. The KiSS-1/GPR54 system stimulates the gonadotrophin releasing hormone (GnRH) neurons and is involved in the feedback regulation of the HPG axis by gonadal steroids. Different hypothalamic nuclei are involved in negative (arcuate nucleus; ARC) and positive (anteroventral periventricular nucleus; AVPV) feedback in mice. Continuous administration of kisspeptins down-regulates the HPG axis. During pregnancy, kisspeptins are secreted from the placenta in large amounts and are responsible for the physiological invasion of primary human trophoblast. Kisspeptins have been administered to normal male and female individuals as well as to women with hypothalamic secondary amenorrhoea. In all cases, gonadotrophin secretion was potently stimulated. Kisspeptin antagonists have been synthesized to successfully suppress GnRH and gonadotrophin release. These agonists and antagonists appear as valuable new tools for manipulating the HPG axis and are promising drugs for future treatment. The scope of this review highlights the role of kisspeptins in regulating gonadotrophin secretion and explores their possible therapeutic use.

Topics: Adult; Animals; Female; Gene Expression Regulation; Gonadal Disorders; Gonadotropins; Humans; Hypogonadism; Kisspeptins; Male; Mice; Mutation; Pregnancy; Rats; Receptors, G-Protein-Coupled; Receptors, Kisspeptin-1