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A direct androgenic involvement in the expression of human corticotropin-releasing hormone.

Bao, A.-M. and Fischer, D.F. and Wu, Y.-H. and Hol, E.M. and Balesar, R. and Unmehopa, U.A. and Zhou, J.-N. and Swaab, D.F. (2006) A direct androgenic involvement in the expression of human corticotropin-releasing hormone. Molecular psychiatry, 11(6), 567-576. ISSN 13594184. doi: 10.1038/sj.mp.4001800.

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Abstract

We investigated the possibility of a direct action of androgens on the expression of the human corticotropin-releasing hormone (CRH), which plays a central role in the hypothalamic-pituitary-adrenal (HPA)-axis. Colocalization of CRH and nuclear/cytoplasmic androgen receptor (AR) was found in neurons of the paraventricular nucleus (PVN) in the human hypothalamus. A potential androgen-responsive element (ARE) in the human CRH promoter was subsequently analyzed with bandshifts and cotransfections in neuroblastoma cells. In the presence of testosterone, recombinant human AR bound specifically to the CRH-ARE. Expression of AR in combination with testosterone repressed CRH promoter activity through the ARE. We conclude that androgens may directly affect CRH neurons in the human PVN via AR binding to the CRH-ARE, which may have consequences for sex-specific pathogenesis of mood disorders.

Item Type:Article
Additional Information:doi: 10.1038/sj.mp.4001800
Institutes:Netherlands Institute for Neuroscience (NIN)
ID Code:3711
Deposited On:13 Feb 2009 17:14
Last Modified:10 Dec 2009 13:14

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