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

AM Bao, DF Fischer, YH Wu, EM Hol, R Balesar…�- Molecular�…, 2006 - nature.com
AM Bao, DF Fischer, YH Wu, EM Hol, R Balesar, UA Unmehopa, JN Zhou, DF Swaab
Molecular psychiatry, 2006nature.com
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�…
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.
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