Kisspeptin Neurons in the Ovine Arcuate Nucleus and Preoptic Area Are Involved in the Preovulatory Luteinizing Hormone Surge

Abstract

Kisspeptin is the product of the Kiss1 gene that regulates GnRH secretion. In sheep, Kiss1 mRNA-expressing cells are found in the preoptic area (POA) and arcuate nucleus (ARC), and expression is up-regulated in the caudal ARC during the periovulatory period. We hypothesized that kisspeptin neurons in the ARC are activated by estradiol-17beta prior to the preovulatory LH surge. Ovariectomized ewes were treated as follows: 1) estradiol-17beta implants (sc 2 wk) to cause tonic negative feedback; 2) vehicle (no estrogen negative or positive feedback); or 3) positive feedback/GnRH surge-inducing injection of estradiol-17beta (50 microg iv). For groups 2 and 3, brains were collected 1 h after treatment and kisspeptin/Fos immunoreactivity was examined. In the caudal and mid-ARC, the percentage of kisspeptin cells that were Fos immunoreactive increased after acute estradiol treatment (group 3) over that seen in the other two groups. Kisspeptin/Fos colocalization was also quantified in ewes during the luteal and late-follicular phase of the estrous cycle, showing a trend toward an increase in colocalization in the late-follicular phase. Kisspeptin/Fos colocalization was similar in the POA across groups in both experiments. Analysis of Kiss1 mRNA by in situ hybridization revealed an increase in expression during the late-follicular phase in the caudal ARC and POA. These data suggest kisspeptin neurons located in the caudal extent of the ARC are involved in generating the positive feedback preovulatory GnRH/LH surge in the ewe, but there may also be a role for Kiss1-expressing cells in the POA.

Timing and completion of puberty in female mice depend on estrogen receptor α-signaling in kisspeptin neurons

“…Kisspeptin expression increases throughout puberty in mice, rat, sheep, and monkeys, and previous studies have demonstrated that this is an estrogen-dependent phenom- enon (20,22,30,31). Estrogen therapy has been used successfully to jumpstart sexual maturation in girls with constitutive delay of puberty (32), suggesting ER-dependent neurotropic mechanisms governing maturation of central neuronal circuitries that control GnRH release.…”

Kisspeptin activates the hypothalamic–adenohypophyseal–gonadal axis in prepubertal ewe lambs

“…In sheep, the involvement of POA kisspeptin neurons in the E 2 positive feedback is less clear. Recent observations suggest that kisspeptin neurons in the caudal arcuate nucleus are involved in the E 2 positive feedback (Smith et al 2009a). Nevertheless, kisspeptin neurons in the POA of sheep may also be involved in the preovulatory surge of GNRH/LH, because KISS1 expression increases in the POA of ewes just before ovulation.…”

Localization of kisspeptin neurons in the hypothalamus of peripubertal female lambs; possible connection with gonadotrophin releasing hormone and neuropeptide Y neurons

“…The expression of Kiss1 mRNA is also activated in the ARC nucleus of ewe lambs during juvenile development from 25-35 weeks of age (Redmond et al, 2011). It was demonstrated on ovariectomized ewes treated acutely with E2 that the number of kp arcuate cells co-labelled with c-fos increased 6-fold, so the authors conclude that these kp neurons are involved in generating the positive feedback preovulatory GnRH/LH surge (Smith et al, 2009b). It was also demonstrated that mainly the subpopulation of arcuate kp neurons is involved in the increased input to GnRH neurons leading to puberty in sheep (Redmond et al, 2011).…”