The Role of Central Androgen Receptor Actions in Regulating the Hypothalamic-Pituitary-Ovarian Axis

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...

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Veröffentlicht in:Neuroendocrinology 2018-01, Vol.106 (4), p.389-400
Hauptverfasser: Walters, Kirsty A., Edwards, Melissa C., Tesic, Dijana, Caldwell, Aimee S.L., Jimenez, Mark, Smith, Jeremy T., Handelsman, David J.
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container_end_page 400
container_issue 4
container_start_page 389
container_title Neuroendocrinology
container_volume 106
creator Walters, Kirsty A.
Edwards, Melissa C.
Tesic, Dijana
Caldwell, Aimee S.L.
Jimenez, Mark
Smith, Jeremy T.
Handelsman, David J.
description 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.
doi_str_mv 10.1159/000487762
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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.]]></description><identifier>ISSN: 0028-3835</identifier><identifier>EISSN: 1423-0194</identifier><identifier>DOI: 10.1159/000487762</identifier><identifier>PMID: 29635226</identifier><language>eng</language><publisher>Basel, Switzerland: S. 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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.]]></abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>29635226</pmid><doi>10.1159/000487762</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-1504-9734</orcidid><orcidid>https://orcid.org/0000-0002-4200-7476</orcidid></addata></record>
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subjects Androgens
Animals
Brain
Estrous Cycle - metabolism
Female
Glycoproteins
Gonadotropins
Hormones
Hypothalamo-Hypophyseal System - metabolism
Luteinizing hormone
Messenger RNA
Mice
Mice, Knockout
Neurons
Oophorectomy
Original Paper
Ovarian Follicle - metabolism
Ovarian Follicle - pathology
Ovary - metabolism
Ovary - pathology
Pituitary hormones
Receptors, Androgen - metabolism
RNA
title The Role of Central Androgen Receptor Actions in Regulating the Hypothalamic-Pituitary-Ovarian Axis
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