Lim Patrick, Allan Charles M, Notini Amanda J, Axell Anna-Maree, Spaliviero Jennifer, Jimenez Mark, Davey Rachel, McManus Julie, MacLean Helen E, Zajac Jeffrey D, Handelsman David J
Andrology Laboratory, ANZAC Research Institute, Concord Hospital and University of Sydney, Australia.
Reprod Fertil Dev. 2008;20(8):861-70. doi: 10.1071/rd08144.
Spermatogenesis requires androgen but, paradoxically, oestradiol (E2) treatment stimulates spermatogenic development in gonadotrophin- and androgen-deficient hypogonadal (hpg) mice. The mechanisms of E2-induced spermatogenesis were investigated by determining intratesticular E2 levels and testis cell populations in E2-treated hpg male mice, and E2 spermatogenic actions were determined in androgen receptor-knockout (ARKO) mice. Despite increased serum E2 concentrations (150-300 pmol L(-1)), intratesticular E2 concentrations declined fivefold (P < 0.001) in E2-treated v. untreated hpg male mice. Serum FSH reached 40% of normal and total testicular numbers of known FSH-responsive Sertoli, spermatogonia and meiotic spermatocyte populations were significantly (P < 0.001) elevated 1.7-, 4- and 13-fold, respectively. However, E2 administration also increased androgen-dependent pachytene spermatocytes and post-meiotic spermatids to levels comparable with testosterone-treated hpg testes. Selective investigation of androgen receptor involvement used E2-treated ARKO mice, which were found to exhibit increased (1.6-fold; P < 0.05) intratesticular E2 concentrations and suppression of the elevated serum gonadotrophins, although FSH remained twofold higher than normal. However, testis size and total Sertoli, spermatogonia and spermatocyte numbers were not increased in E2-treated ARKO male mice. Therefore, E2-stimulated murine spermatogenic development occurs with markedly suppressed and not elevated intratesticular E2 levels and displays an absolute requirement for functional androgen receptors. We propose that this paradoxical E2 spermatogenic response is explained by predominantly extratesticular E2 actions, increasing FSH to combine with residual androgen activity in hpg testes to stimulate pre- to post-meiotic development.
精子发生需要雄激素，但矛盾的是，雌二醇（E2）处理可刺激促性腺激素和雄激素缺乏的性腺功能减退（hpg）小鼠的精子发生发育。通过测定E2处理的hpg雄性小鼠的睾丸内E2水平和睾丸细胞群体，研究了E2诱导精子发生的机制，并在雄激素受体敲除（ARKO）小鼠中确定了E2的精子发生作用。尽管E2处理的hpg雄性小鼠血清E2浓度升高（150 - 300 pmol L(-1)），但睾丸内E2浓度在E2处理组与未处理组相比下降了五倍（P < 0.001）。血清促卵泡激素（FSH）达到正常水平的40%，已知对FSH有反应的支持细胞、精原细胞和减数分裂期精母细胞群体的睾丸总数分别显著升高（P < 0.001），分别为1.7倍、4倍和13倍。然而，给予E2也使雄激素依赖性的粗线期精母细胞和减数分裂后精子细胞增加到与睾酮处理的hpg睾丸相当的水平。对雄激素受体参与情况的选择性研究使用了E2处理的ARKO小鼠，发现其睾丸内E2浓度升高（1.6倍；P < 0.05），血清促性腺激素升高受到抑制，尽管FSH仍比正常水平高两倍。然而，E2处理的ARKO雄性小鼠的睾丸大小以及支持细胞、精原细胞和精母细胞的总数并未增加。因此，E2刺激的小鼠精子发生发育是在睾丸内E2水平显著抑制而非升高的情况下发生的，并且对功能性雄激素受体表现出绝对需求。我们提出，这种矛盾的E2精子发生反应主要由睾丸外E2作用来解释，即增加FSH以与hpg睾丸中的残余雄激素活性相结合，从而刺激减数分裂前到减数分裂后的发育。
