| First Author | Dubois SL | Year | 2016 |
| Journal | Endocrinology | Volume | 157 |
| Issue | 4 | Pages | 1546-54 |
| PubMed ID | 26824364 | Mgi Jnum | J:234031 |
| Mgi Id | MGI:5788808 | Doi | 10.1210/en.2015-1923 |
| Citation | Dubois SL, et al. (2016) Estradiol Restrains Prepubertal Gonadotropin Secretion in Female Mice via Activation of ERalpha in Kisspeptin Neurons. Endocrinology 157(4):1546-54 |
| abstractText | Elimination of estrogen receptoralpha (ERalpha) from kisspeptin (Kiss1) neurons results in premature LH release and pubertal onset, implicating these receptors in 17beta-estradiol (E2)-mediated negative feedback regulation of GnRH release during the prepubertal period. Here, we tested the dependency of prepubertal negative feedback on ERalpha in Kiss1 neurons. Prepubertal (postnatal d 14) and peripubertal (postnatal d 34) wild-type (WT) and Kiss1 cell-specific ERalpha knockout (KERalphaKO) female mice were sham operated or ovariectomized and treated with either vehicle- or E2-containing capsules. Plasma and tissues were collected 2 days after surgery for analysis. Ovariectomy increased LH and FSH levels, and E2 treatments completely prevented these increases in WT mice of both ages. However, in prepubertal KERalphaKO mice, basal LH levels were elevated vs WT, and both LH and FSH levels were not further increased by ovariectomy or affected by E2 treatment. Similarly, Kiss1 mRNA levels in the medial basal hypothalamus, which includes the arcuate nucleus, were suppressed with E2 treatment in ovariectomized prepubertal WT mice but remained unaffected by any treatment in KERalphaKO mice. In peripubertal KERalphaKO mice, basal LH and FSH levels were not elevated vs WT and were unaffected by ovariectomy or E2. In contrast to our previous findings in adult animals, these results demonstrate that suppression of gonadotropins and Kiss1 mRNA by E2 in prepubertal animals depends upon ERalpha activation in Kiss1 neurons. Our observations are consistent with the hypothesis that these receptors play a critical role in restraining GnRH release before the onset and completion of puberty. |
