| First Author | Novaira HJ | Year | 2018 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 315 |
| Issue | 5 | Pages | E1019-E1033 |
| PubMed ID | 30040478 | Mgi Jnum | J:273855 |
| Mgi Id | MGI:6283154 | Doi | 10.1152/ajpendo.00173.2018 |
| Citation | Novaira HJ, et al. (2018) Impairments in the reproductive axis of female mice lacking estrogen receptor beta in GnRH neurons. Am J Physiol Endocrinol Metab 315(5):E1019-E1033 |
| abstractText | The effect of estrogen on the differentiation and maintenance of reproductive tissues is mediated by two nuclear estrogen receptors (ERs), ERalpha, and ERbeta. Lack of functional ERalpha and ERbeta genes in vivo significantly affects reproductive function; however, the target tissues and signaling pathways in the hypothalamus are not clearly defined. Here, we describe the generation and reproductive characterization of a complete-ERbeta KO (CERbetaKO) and a GnRH neuron-specific ERbetaKO (GERbetaKO) mouse models. Both ERbetaKO mouse models displayed a delay in vaginal opening and first estrus. Hypothalamic gonadotropin-releasing hormone (GnRH) mRNA expression levels in both ERbetaKO mice were similar to control mice; however female CERbetaKO and GERbetaKO mice had lower basal and surge serum gonadotropin levels. Although a GnRH stimulation test in both female ERbetaKO models showed preserved gonadotropic function in the same animals, a kisspeptin stimulation test revealed an attenuated response by GnRH neurons, suggesting a role for ERbeta in normal GnRH neuron function. No alteration in estrogen-negative feedback was observed in either ERbetaKO mouse models after ovariectomy and estrogen replacement. Further, abnormal development of ovarian follicles with low serum estradiol levels and impairment of fertility were observed in both ERbetaKO mouse models. In male ERbetaKO mice, no differences in the timing of pubertal onset or serum luteinizing hormone and follicle-stimulating hormone levels were observed as compared with controls. Taken together, these data provide in vivo evidence for a role of ERbeta in GnRH neurons in modulating puberty and reproduction, specifically through kisspeptin responsiveness in the female hypothalamic-pituitary-gonadal axis. |
