4.5 Article

Spatiotemporal expression of androgen receptors in the female rat brain during the oestrous cycle and the impact of exogenous androgen administration: A comparison with gonadally intact males

Journal

MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 321, Issue 2, Pages 161-174

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2010.02.029

Keywords

Androgen receptor; Dihydrotestosterone; The oestrous cycle; Brain

Funding

  1. Swedish Medical Research Council [5859, 10380, 2008-72VP-15445-01A]
  2. Sahlgrenska Academy Research Council
  3. Fred G. and Emma E. Kanolds Stiftelse, Anna Cederbergs Stiftelse, Fredrik and Ingrid Thurings Stiftelse and Hjalmar Svenssons Research Foundation
  4. Chinese Special Fund [200801170]

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Little is known about the regulation and cellular distribution of androgen receptors (ARs) in female rodent brains at various stages of the oestrous cycle. This information is critical for further studies of androgen signalling in the regulation of brain function under physiological and pathophysiological conditions In this report, we show that the distribution of AR immunoreactivity in the female rat brain is consistent with reported AR mRNA hybridisation signals in the male brain, except for the dentate gyrus of the hippocampus Immunohistochemical and Western blot analyses performed herein revealed that the onset of region-specific changes in AR proteins was strongly correlated with circulating and ovarian levels of estradiol and testosterone across the oestrous cycle. During the metestrus and diestrus stages, however, the highest levels of AR expression were abolished by chronic dihydrotestosterone (DHT) treatment. This demonstrates that fluctuations in endogenous androgens are required for the regulation of AR expression in the female rat brain Colocalisation studies revealed that. (1) anatomical variations in AR protein localisation existed between female and male brains, (2) AR immunoreactivity was both neuronal and non-neuronal, and (3) AR protein expression was lower in female rat brains at all stages of the oestrous cycle compared to age-matched males Our results indicate the presence of regional sex differences in AR expression and changes in the proportion of AR between different subcellular compartments. Furthermore. DHT was found to down-regulate the level of AR in the subcellular compartment in females in a region-specific manner As a whole, the present study provides the first step toward understanding the dynamics of AR expression and regulation in the brain during normal physiological conditions and for differences in neuronal androgen effects based on sex (C) 2010 Elsevier Ireland Ltd. All rights reserved.

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