Maninger Nicole, Wolkowitz Owen M, Reus Victor I, Epel Elissa S, Mellon Synthia H
Department of Psychiatry, University of California San Francisco, School of Medicine, San Francisco 94143, USA.
Front Neuroendocrinol. 2009 Jan;30(1):65-91. doi: 10.1016/j.yfrne.2008.11.002. Epub 2008 Dec 3.
DHEA and DHEAS are steroids synthesized in human adrenals, but their function is unclear. In addition to adrenal synthesis, evidence also indicates that DHEA and DHEAS are synthesized in the brain, further suggesting a role of these hormones in brain function and development. Despite intensifying research into the biology of DHEA and DHEAS, many questions concerning their mechanisms of action and their potential involvement in neuropsychiatric illnesses remain unanswered. We review and distill the preclinical and clinical data on DHEA and DHEAS, focusing on (i) biological actions and putative mechanisms of action, (ii) differences in endogenous circulating concentrations in normal subjects and patients with neuropsychiatric diseases, and (iii) the therapeutic potential of DHEA in treating these conditions. Biological actions of DHEA and DHEAS include neuroprotection, neurite growth, and antagonistic effects on oxidants and glucocorticoids. Accumulating data suggest abnormal DHEA and/or DHEAS concentrations in several neuropsychiatric conditions. The evidence that DHEA and DHEAS may be fruitful targets for pharmacotherapy in some conditions is reviewed.
脱氢表雄酮(DHEA)和硫酸脱氢表雄酮(DHEAS)是在人体肾上腺中合成的类固醇,但它们的功能尚不清楚。除了肾上腺合成外,有证据还表明DHEA和DHEAS在大脑中也有合成,这进一步表明这些激素在脑功能和发育中发挥作用。尽管对DHEA和DHEAS生物学特性的研究不断深入,但许多关于它们的作用机制以及它们在神经精神疾病中潜在作用的问题仍未得到解答。我们回顾并提炼了关于DHEA和DHEAS的临床前和临床数据,重点关注:(i)生物学作用和假定的作用机制;(ii)正常受试者和神经精神疾病患者内源性循环浓度的差异;(iii)DHEA治疗这些疾病的潜在可能性。DHEA和DHEAS的生物学作用包括神经保护、神经突生长以及对氧化剂和糖皮质激素的拮抗作用。越来越多的数据表明,在几种神经精神疾病中DHEA和/或DHEAS浓度异常。本文综述了DHEA和DHEAS在某些情况下可能成为药物治疗有效靶点的证据。