Sexual Dimorphism in Kisspeptin Signaling

Abstract

Kisspeptin (KP) and kisspeptin receptor (KPR) are essential for the onset of puberty, development of gonads, and maintenance of gonadal function in both males and females. Hypothalamic KPs and KPR display a high degree of sexual dimorphism in expression and function. KPs act on KPR in gonadotropin releasing hormone (GnRH) neurons and induce distinct patterns of GnRH secretion in males and females. GnRH acts on the anterior pituitary to secrete gonadotropins, which are required for steroidogenesis and gametogenesis in testes and ovaries. Gonadal steroid hormones in turn regulate the KP neurons. Gonadal hormones inhibit the KP neurons within the arcuate nucleus and generate pulsatile GnRH mediated gonadotropin (GPN) secretion in both sexes. However, the numbers of KP neurons in the anteroventral periventricular nucleus and preoptic area are greater in females, which release a large amount of KPs in response to a high estrogen level and induce the preovulatory GPN surge. In addition to the hypothalamus, KPs and KPR are also expressed in various extrahypothalamic tissues including the liver, pancreas, fat, and gonads. There is a remarkable difference in circulating KP levels between males and females. An increased level of KPs in females can be linked to increased numbers of KP neurons in female hypothalamus and more KP production in the ovaries and adipose tissues. Although the sexually dimorphic features are well characterized for hypothalamic KPs, very little is known about the extrahypothalamic KPs. This review article summarizes current knowledge regarding the sexual dimorphism in hypothalamic as well as extrahypothalamic KP and KPR system in primates and rodents.

Serum kisspeptin and proopiomelanocortin in cystic fibrosis: a single study

“…KISS is involved in the regulation of puberty onset, ovarian function, trophoblast invasion, fertility regulation, pregnancy and lactation 23 . In addition to the hypothalamus, KISS and the KISS receptor are also expressed in various extrahypothalamic tissues, including the liver, pancreas, fat and gonads 24 . Consequently, the role of KISS in the reproductive process is fairly well characterized, however, it also has metabolic functions, including effects on appetite and nutritional behavior 25 , 26 .…”

“…A significant difference in circulating KISS levels between males and females was previously reported. An increased level of KISS in healthy females may be associated with a higher number of KISS neurons in the female hypothalamus and increased KISS production in the ovaries and adipose tissues 24 . The lack of difference in KISS levels may be due to low body fat and ovarian dysfunction in females with CF 9 .…”

“…Gonadotropin releasing hormone acts on the gonadotrophs in the anterior pituitary gland to release follicle stimulating hormone and luteinizing hormone into the systemic circulation. The gonadotrophins then stimulate the gonads to release testosterone in males, and oestradiol as well as progesterone in females 24 , 36 . Hence, it seems reasonable to analyze KISS and other hormones simultaneously.…”

Kisspeptin modulates sex-like phenotypes in the neonatal period

“…Over the past few years, the knowledge about the biological role in kisspeptin (Kiss1) has advanced namely in shaping the sexual differentiation of the brain (Lee et al, 2022). This peptide family shows predominant expression in the hypothalamus, wherein these peptides play a crucial role in regulating gonadotrophin-releasing hormone (GnRH) (Lee et al, 2022; Oakley et al, 2009).…”

“…Over the past few years, the knowledge about the biological role in kisspeptin (Kiss1) has advanced namely in shaping the sexual differentiation of the brain (Lee et al, 2022). This peptide family shows predominant expression in the hypothalamus, wherein these peptides play a crucial role in regulating gonadotrophin-releasing hormone (GnRH) (Lee et al, 2022; Oakley et al, 2009). Notably, Kiss1 neurons in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) are regulated by estrogen and estradiol, serving as pivotal elements inside the sexual hormone feedback loop (Oakley et al, 2009).…”