ANZAC Research Institute, Sydney, New South Wales 2139, Australia.
Endocrinology. 2010 Jun;151(6):2800-10. doi: 10.1210/en.2009-1477. Epub 2010 Apr 21.
Both testosterone and its nonaromatizable metabolite dihydrotestosterone (DHT) induce spermatogenesis in gonadotropin-deficient hpg mice. Surprisingly, because aromatization is not required, estradiol (E2) also induces spermatogenesis and increases circulating FSH in hpg mice, but the mechanism remains unclear. We studied E2-induced spermatogenesis in hpg mice on an estrogen receptor (ER)-alpha (hpg/alphaERKO) or ERbeta (hpg/betaERKO) knockout or wild-type ER (hpg/WT) background treated with subdermal E2 or DHT implants for 6 wk. In hpg/WT and hpg/betaERKO, but not hpg/alphaERKO mice, E2 increased testis and epididymal weight, whereas DHT-induced increases were unaffected by ERalpha or ERbeta inactivation. E2 but not DHT treatment increased serum FSH (but not LH) in hpg/WT and hpg/betaERKO but not hpg/alphaERKO hpg mice. DHT or E2 alone increased (premeiotic) spermatogonia and (meiotic) spermatocytes without significant change in Sertoli cell numbers. DHT alone increased postmeiotic spermatids, regardless of ER presence, compared with variable ERalpha-dependent E2 postmeiotic responses. An ERalpha-mediated effect was confirmed by treating hpg mice for 6 wk by subdermal selective ER-alpha (16alpha-LE(2)) or ERbeta (8beta-VE(2)) agonist implants. ERalpha (but not ERbeta) agonist increased testis and epididymal weight, Sertoli cell, spermatogonia, meiotic, and postmeiotic germ cell numbers. Only ERalpha agonist markedly increased serum FSH, whereas either agonist induced small rises in serum LH. Administration of ERalpha agonist or E2 in the presence of functional ERalpha induced prominent gene expression of specific Sertoli (Eppin, Rhox5) and Leydig cell (Cyp11a1, Hsd3b1) markers. We conclude that E2-induced spermatogenesis in hpg mice involves an ERalpha-dependent neuroendocrine mechanism increasing blood FSH and Sertoli cell function.
睾酮及其非芳香化代谢物二氢睾酮（DHT）均可诱导促性腺激素缺乏的 hpg 小鼠精子发生。令人惊讶的是，由于不需要芳香化作用，雌二醇（E2）也可诱导 hpg 小鼠精子发生并增加循环 FSH，但机制尚不清楚。我们研究了 E2 诱导的 hpg 小鼠的精子发生，这些小鼠在雌激素受体（ER）-α（hpg/alphaERKO）或 ERβ（hpg/betaERKO）敲除或野生型 ER（hpg/WT）背景下接受皮下 E2 或 DHT 植入物治疗 6 周。在 hpg/WT 和 hpg/betaERKO 小鼠中，但在 hpg/alphaERKO 小鼠中，E2 增加了睾丸和附睾的重量，而 DHT 诱导的增加不受 ERα或 ERβ失活的影响。E2 但不是 DHT 处理增加了 hpg/WT 和 hpg/betaERKO 但不是 hpg/alphaERKO hpg 小鼠的血清 FSH（但不是 LH）。DHT 或 E2 单独增加（减数分裂前）精原细胞和（减数分裂）精母细胞，而 Sertoli 细胞数量没有明显变化。DHT 单独增加减数分裂后精子，无论 ER 存在与否，与可变的 ERα依赖性 E2 减数分裂后反应相比。通过皮下选择性 ER-α（16α-LE（2））或 ERβ（8β-VE（2））激动剂植入物治疗 hpg 小鼠 6 周，证实了 ERα 介导的作用。ERα（但不是 ERβ）激动剂增加了睾丸和附睾的重量、Sertoli 细胞、精原细胞、减数分裂和减数分裂后生殖细胞的数量。只有 ERα 激动剂显著增加了血清 FSH，而任何一种激动剂都引起了血清 LH 的轻微升高。在有功能性 ERα 的情况下给予 ERα 激动剂或 E2 诱导了特定 Sertoli（Eppin、Rhox5）和 Leydig 细胞（Cyp11a1、Hsd3b1）标志物的明显基因表达。我们的结论是，E2 诱导的 hpg 小鼠精子发生涉及 ERα 依赖性神经内分泌机制，增加了血液 FSH 和 Sertoli 细胞功能。
