Dharia Sejal, Parker C Richard
Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama 35294-7333, USA.
Semin Reprod Med. 2004 Nov;22(4):361-8. doi: 10.1055/s-2004-861552.
Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) are the principal C19 steroids produced by the human adrenals. Their plasma levels decline to less than 20% of their maximal value during aging. Because these steroids appear to play a role in the maintenance of immunity, musculoskeletal integrity, and cardiovascular health, age-associated declines in adrenal androgen production may contribute to decreased immune function, osteoporosis, and atherosclerosis. Production of DHEA and DHEAS has been localized to the zona reticularis (ZR) of the adrenal cortex and can be modulated by intra-adrenal or extra-adrenal modulators. Extra-adrenal modulators include corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), insulin, and transforming growth factor beta (TGF-beta). Intra-adrenal regulators include enzymes and proteins involved in the steroidogenic pathway, specifically 17,20 lyase activity and DHEA sulfotransferase (DST). The natural histories of the emergence of adrenal androgen production and the ontogeny of the ZR appear to correlate closely. In addition, aging results in a decline in adrenal androgen production, and our data suggest a parallel diminution in the area represented by the ZR. This decline in the ZR may result from apoptosis, cellular and humoral immunity, or a reduction in the replicative capacity of the cells of the ZR.
脱氢表雄酮（DHEA）和硫酸脱氢表雄酮（DHEAS）是人体肾上腺产生的主要C19类固醇。在衰老过程中，它们的血浆水平降至最大值的20%以下。由于这些类固醇似乎在维持免疫、肌肉骨骼完整性和心血管健康方面发挥作用，肾上腺雄激素产生随年龄的下降可能导致免疫功能下降、骨质疏松和动脉粥样硬化。DHEA和DHEAS的产生已定位到肾上腺皮质的网状带（ZR），并且可以受到肾上腺内或肾上腺外调节剂的调节。肾上腺外调节剂包括促肾上腺皮质激素释放激素（CRH）、促肾上腺皮质激素（ACTH）、胰岛素和转化生长因子β（TGF-β）。肾上腺内调节剂包括参与类固醇生成途径的酶和蛋白质，特别是17,20裂解酶活性和DHEA硫酸转移酶（DST）。肾上腺雄激素产生的出现和ZR的个体发生的自然史似乎密切相关。此外，衰老导致肾上腺雄激素产生下降，我们的数据表明ZR所代表的面积也相应减少。ZR的这种下降可能是由于细胞凋亡、细胞和体液免疫，或者ZR细胞复制能力的降低。
