Impairments in the reproductive axis of female mice lacking estrogen receptor β in GnRH neurons
| Autor: | Silvia Capellino, Horacio J. Novaira, Sally Radovick, Fredric E. Wondisford, Andrew Schoeffield, Jon E. Levine, Ariel L Negron, Jones Bernardes Graceli, Gloria E. Hoffman, Andrew Wolfe |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty Physiology medicine.drug_class Endocrinology Diabetes and Metabolism Hypothalamus Estrogen receptor Biology Gonadotropin-Releasing Hormone Mice 03 medical and health sciences In vivo Physiology (medical) Internal medicine medicine Animals Estrogen Receptor beta Sexual Maturation Gene Feedback Physiological Mice Knockout Neurons Estradiol Luteinizing Hormone Fertility 030104 developmental biology Endocrinology Estrogen Female Follicle Stimulating Hormone hormones hormone substitutes and hormone antagonists Research Article |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 315:E1019-E1033 |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.00173.2018 |
| Popis: | The effect of estrogen on the differentiation and maintenance of reproductive tissues is mediated by two nuclear estrogen receptors (ERs), ERα, and ERβ. Lack of functional ERα and ERβ 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-ERβ KO (CERβKO) and a GnRH neuron-specific ERβKO (GERβKO) mouse models. Both ERβKO mouse models displayed a delay in vaginal opening and first estrus. Hypothalamic gonadotropin-releasing hormone (GnRH) mRNA expression levels in both ERβKO mice were similar to control mice; however female CERβKO and GERβKO mice had lower basal and surge serum gonadotropin levels. Although a GnRH stimulation test in both female ERβKO models showed preserved gonadotropic function in the same animals, a kisspeptin stimulation test revealed an attenuated response by GnRH neurons, suggesting a role for ERβ in normal GnRH neuron function. No alteration in estrogen-negative feedback was observed in either ERβKO 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 ERβKO mouse models. In male ERβKO 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 ERβ in GnRH neurons in modulating puberty and reproduction, specifically through kisspeptin responsiveness in the female hypothalamic-pituitary-gonadal axis. |
| Databáze: | OpenAIRE |
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