Goodarzi Mark O, Carmina Enrico, Azziz Ricardo
Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
University of Palermo, Palermo, Italy.
J Steroid Biochem Mol Biol. 2015 Jan;145:213-25. doi: 10.1016/j.jsbmb.2014.06.003. Epub 2014 Jul 5.
Approximately 20-30% of PCOS women demonstrate excess adrenal precursor androgen (APA) production, primarily using DHEAS as a marker of APA in general and more specifically DHEA, synthesis. The role of APA excess in determining or causing PCOS is unclear, although observations in patients with inherited APA excess (e.g., patients with 21-hydroxylase deficient congenital classic or non-classic adrenal hyperplasia) demonstrate that APA excess can result in a PCOS-like phenotype. Inherited defects of the enzymes responsible for steroid biosynthesis, or defects in cortisol metabolism, account for only a very small fraction of women suffering from hyperandrogenism or APA excess. Rather, women with PCOS and APA excess appear to have a generalized exaggeration in adrenal steroidogenesis in response to ACTH stimulation, although they do not have an overt hypothalamic-pituitary-adrenal axis dysfunction. In general, extra-adrenal factors, including obesity, insulin and glucose levels, and ovarian secretions, play a limited role in the increased APA production observed in PCOS. Substantial heritabilities of APAs, particularly DHEAS, have been found in the general population and in women with PCOS; however, the handful of SNPs discovered to date account only for a small portion of the inheritance of these traits. Paradoxically, and as in men, elevated levels of DHEAS appear to be protective against cardiovascular risk in women, although the role of DHEAS in modulating this risk in women with PCOS remains unknown. In summary, the exact cause of APA excess in PCOS remains unclear, although it may reflect a generalized and inherited exaggeration in androgen biosynthesis of an inherited nature.
大约20%-30%的多囊卵巢综合征（PCOS）女性表现出肾上腺前体雄激素（APA）分泌过多，一般主要将硫酸脱氢表雄酮（DHEAS）作为APA的标志物，更具体地说是将脱氢表雄酮（DHEA）的合成作为标志物。虽然在遗传性APA分泌过多的患者（例如21-羟化酶缺乏的先天性典型或非典型肾上腺皮质增生患者）中的观察表明，APA分泌过多可导致类似PCOS的表型，但APA分泌过多在决定或导致PCOS方面的作用尚不清楚。负责类固醇生物合成的酶的遗传性缺陷，或皮质醇代谢缺陷，仅占患有高雄激素血症或APA分泌过多女性的极小部分。相反，患有PCOS且APA分泌过多的女性似乎在促肾上腺皮质激素（ACTH）刺激下肾上腺类固醇生成普遍增强，尽管她们没有明显的下丘脑-垂体-肾上腺轴功能障碍。一般来说，包括肥胖、胰岛素和血糖水平以及卵巢分泌物在内的肾上腺外因素，在PCOS患者中观察到的APA分泌增加中起有限作用。在普通人群和PCOS女性中已发现APAs，尤其是DHEAS具有较高的遗传度；然而，迄今为止发现的少数单核苷酸多态性（SNP）仅占这些性状遗传的一小部分。矛盾的是，与男性一样，DHEAS水平升高似乎对女性心血管风险具有保护作用，尽管DHEAS在调节PCOS女性这种风险中的作用尚不清楚。总之，PCOS中APA分泌过多的确切原因尚不清楚，尽管它可能反映了雄激素生物合成中一种遗传性的普遍且遗传性增强。
