Role of kisspeptin neurons as a GnRH surge generator: Comparative aspects in rodents and non‐rodent mammals

Abstract

Ovulation is an essential phenomenon for reproduction in mammalian females along with follicular growth. It is well established that gonadal function is controlled by the neuroendocrine system called the hypothalamus-pituitary-gonadal (HPG) axis. Gonadotropin-releasing hormone (GnRH) neurons, localized in the hypothalamus, had been considered to be the head in governing the HPG axis for a long time until the discovery of kisspeptin. In females, induction of ovulation and folliculogenesis has been linked to a surge mode and pulse mode of GnRH releases, respectively. The mechanisms of how the two modes of GnRH are differently regulated had long remained elusive. The discovery of kisspeptin neurons, distributed in two hypothalamic nuclei, such as the arcuate nucleus in the caudal hypothalamus and preoptic area or the anteroventral periventricular nucleus in the rostral hypothalamic regions, and analyses of the detailed functions of kisspeptin neurons have led marked progress on the understanding of different mechanisms regulating GnRH surges (ovulation) and GnRH pulses (folliculogenesis). The present review will focus on the role of kisspeptin neurons as the GnRH surge generator, including the sexual differentiation of the surge generation system and factors that regulate the surge generator. Comparative aspects between mammalian species are especially focused on.

Estrogen increases <i>KISS1</i> expression in newly generated immortalized <i>KISS1</i>-expressing cell line derived from goat preoptic area

“…Importantly, the response of GP64 cells to E2 was opposite to that of GA28 cells, a goat KNDy neuron cell line, whose KISS1 expression was significantly suppressed by E2 treatment [43]. In addition, the GP64 cells showed an expression of kisspeptin and ERα at the The POA/AVPV kisspeptin neurons are indicated to be direct targets of estrogen positive feedback [29,30,35,47,48], which is one of the most important characteristics of the neurons to induce GnRH/LH surge in female mammals. Previous in vivo studies have demonstrated that E2 treatment increased KISS1 expression in AVPV kisspeptin neurons in rodents [28,31].…”

“…The number of POA kisspeptin neurons co-expressing c-Fos, a marker for neuronal activation, increased at the time of LH surge in ewes [32], and the high 17βestradiol (E2) treatment increased the number of c-Fos-positive POA kisspeptin neurons in goats and monkeys [22,33]. Thus, the POA/AVPV kisspeptin neurons are assumed to be a direct target of estrogen positive feedback and the central ovulation regulator [34,35].…”

Chronic exposure to perfluorohexane sulfonate leads to a reproduction deficit by suppressing hypothalamic kisspeptin expression in mice

“…The kiss-1 gene expresses kisspeptin and may participate in regulating the HPG axis. Extensive evidence indicates that AVPV-kisspeptin neurons regulate the generation of GnRH and the LH surge, and ARC-kisspeptin neurons are involved in the rhythm of the GnRH pulse [50]. Smith et al analysed kiss-1 mRNA expression in the AVPV and ARC in response to E2 and found that E2 could stimulate AVPV kisspeptin neurons and inhibit ARC kisspeptin neurons [51,52].…”

Chronic Exposure to Perfluorohexane Sulfonate Leads to a Reproduction Deficit by Suppressing Hypothalamic Kisspeptin Expression in Mice

“…The kiss-1 gene expresses kisspeptin and may participate in regulating the HPG axis. An abundance of evidence indicates that AVPV-kisspeptin neurons regulate the generation of GnRH and the LH surge, and ARC-kisspeptin neurons are involved in the rhythm of the GnRH pulse [40]. Smith et al analyzed kiss-1 mRNA expression in the AVPV and ARC in response to E2 and found that E2 could stimulate AVPV kisspeptin neurons and inhibit ARC kisspeptin neurons [41,42].…”