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

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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Acknowledgements

We are indebted to the Netherlands Brain Bank (coordinator Dr R Ravid) at the Netherlands Institute for Brain Research for providing us with brain material. We thank Dr FJH Tilders for the PFU 83 antiserum and DR J Trapman for the hAR expression vector. We wish to thank Mr B Fisser and Ms K Schuuman for their technical assistance, and Mrs WTP Verweij for correcting the English. This investigation was supported by KNAW 02CDP019 and 03CDP001.

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Bao, AM., Fischer, D., Wu, YH. et al. A direct androgenic involvement in the expression of human corticotropin-releasing hormone. Mol Psychiatry 11, 567–576 (2006). https://doi.org/10.1038/sj.mp.4001800

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