The Role of Central Androgen Receptor Actions in Regulating the Hypothalamic-Pituitary-Ovarian Axis
| Autor: | Jeremy Troy Smith, Kirsty A Walters, David J. Handelsman, Melissa C Edwards, Dijana Tesic, Mark Jimenez, Aimee S L Caldwell |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty Hypothalamo-Hypophyseal System medicine.drug_class Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Estrous Cycle Biology 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Mice 0302 clinical medicine Endocrinology Ovarian Follicle Internal medicine medicine Animals Ovarian follicle Estrous cycle Mice Knockout Endocrine and Autonomic Systems Ovary Antral follicle Androgen Androgen receptor 030104 developmental biology medicine.anatomical_structure chemistry Receptors Androgen Female Anteroventral periventricular nucleus Neurokinin B Luteinizing hormone |
| Zdroj: | Neuroendocrinology. 106(4) |
| ISSN: | 1423-0194 |
| Popis: | The androgen receptor (AR) is expressed throughout the hypothalamic-pituitary-gonadal (HPG) axis, and findings from female global AR knockout mice confirm that AR-mediated androgen actions play important roles in regulating female reproductive function. We generated neuron-specific AR knockout mice (NeurARKO) to investigate the functional role of neuronal AR-mediated androgen action in regulating the female HPG axis and fertility. Relative to control females, NeurARKO females exhibited elevated luteinizing hormone (LH) levels at diestrus (p < 0.05) and a compromised serum LH response to ovariectomy and E2 priming (p < 0.01). Furthermore, NeurARKO females displayed reduced Kiss1 mRNA expression in the anteroventral periventricular nucleus at diestrus (p < 0.05) and proestrus (p < 0.05), but elevated Kiss1 (p < 0.05) and neurokinin B (Tac2, p < 0.05) mRNA expression in the arcuate nucleus at proestrus compared to WT controls. Ovarian follicle dynamics were also altered in NeurARKO ovaries at 3 months of age, with a significant reduction in large antral follicle numbers at the proestrus stage compared to control WT ovaries (p < 0.05). Increased follicular atresia was evident in NeurARKO ovaries with a 4-fold increase in unhealthy large preantral follicles (p < 0.01). Despite the findings of aberrant neuroendocrine and ovarian characteristics in the NeurARKO females, estrous cyclicity and overall fertility were comparable between NeurARKO and WT females. In conclusion, our findings revealed that selective loss of neuronal AR actions impacts the kisspeptin/GnRH/LH cascade leading to compromised ovarian follicle dynamics. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|