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

• Published in: Molecular psychiatry Vol. 11; no. 6; pp. 567 - 576
• Main Authors: BAO, A.-M, FISCHER, D. F, WU, Y.-H, HAL, E. M, BALESAR, R, UNMEHOPA, U. A, ZHOU, J.-N, SWAAB, D. F
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.06.2006
• Subjects: Adult; Aged; Aged, 80 and over; Androgen receptors; Androgens; Autopsies; Biochemistry and metabolism; Biological and medical sciences; Brain research; Central nervous system; Corticotropin-releasing hormone; Corticotropin-Releasing Hormone - genetics; Corticotropin-Releasing Hormone - metabolism; Estrogens; Female; Fundamental and applied biological sciences. Psychology; Gender differences; Genomics; Humans; Hypothalamic-pituitary-adrenal axis; Hypothalamus; Male; Middle Aged; Mood Disorders - physiopathology; Neuroblastoma; Neuroblasts; Neuropathology; Neurosciences; Paraventricular Hypothalamic Nucleus - metabolism; Paraventricular nucleus; Pituitary; Receptors, Androgen - metabolism; Regulatory sequences; Response Elements - genetics; Response Elements - physiology; Signal transduction; Testosterone; Testosterone - physiology; Tissue Distribution; Vertebrates: nervous system and sense organs; Netherlands; China; Hypothalamic hormone; Human; hypothalamic-pituitary-adrenal axis; androgen-responsive element; corticotropin-releasing hormone; Androgen; Hypothalamohypophysoadrenal axis; Corticotropin releasing factor; Androgen receptor; Hormone releasing factor; Sex steroid hormone
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/sj.mp.4001800

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.