Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0693, USA.
Steroids. 2013 Mar;78(3):337-40. doi: 10.1016/j.steroids.2012.12.011. Epub 2013 Jan 9.
Estradiol (E2) is the principal physiological estrogen in mammals. E2 and its active metabolites, estrone and estriol have a characteristic phenolic A ring, unlike progesterone, testosterone, cortisol and aldosterone, which have an A ring containing a C3-ketone, a Δ(4) bond and a C19 methyl group. Crystal structures of E2 in the estrogen receptor (ER) confirm the importance of the A ring in stabilizing E2 in the ER. However, other steroids, including Δ(5)-androstenediol, 5α-androstanediol and 27-hydroxycholesterol, which have a saturated A ring containing a 3β-hydroxyl and a C19 methyl group, also mediate physiological responses through binding to estrogen receptor-α (ERα) and ERβ. Moreover, selective estrogen response modulators (SERMs) with diverse structures also regulate transcription of ERα and ERβ. Our understanding of the physiological responses mediated by these "alternative" estrogens is in its infancy. Further studies of the role of these steroids and SERMs in regulating responses mediated by ERα and ERβ a variety of tissues, during different stages of development, are likely to uncover additional estrogenic activities.
雌二醇（E2）是哺乳动物中主要的生理雌激素。E2 及其活性代谢物，雌酮和雌三醇具有特征性的酚 A 环，与孕酮、睾酮、皮质醇和醛固酮不同，后者的 A 环含有 C3-酮、Δ（4）键和 C19 甲基。E2 在雌激素受体（ER）中的晶体结构证实了 A 环在稳定 ER 中 E2 的重要性。然而，其他甾体，包括具有饱和 A 环的Δ（5）-雄烯二醇、5α-雄烷二醇和 27-羟胆固醇，其 A 环含有 3β-羟基和 C19 甲基，也通过与雌激素受体-α（ERα）和 ERβ 结合来介导生理反应。此外，具有不同结构的选择性雌激素受体调节剂（SERMs）也调节 ERα 和 ERβ 的转录。我们对这些“替代”雌激素介导的生理反应的理解还处于起步阶段。进一步研究这些甾体和 SERMs 在调节 ERα 和 ERβ 介导的各种组织在不同发育阶段的反应中的作用，可能会发现更多的雌激素活性。
