Cellular Endocrinology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, JNU Complex, New Delhi 110067, India.
Am J Physiol Endocrinol Metab. 2012 Oct 1;303(7):E886-98. doi: 10.1152/ajpendo.00293.2012. Epub 2012 Jul 31.
FSH and Testosterone (T) regulate spermatogenesis via testicular Sertoli cells (Sc), which bear receptors for these hormones. Despite sufficient circulating levels of FSH and T postnatally, predominant appearance of spermatogonia B and spermatocytes is not discernible until 11 and 18 days of postnatal age, respectively, in rat testes. In an attempt to explore the underlying causes, we cultured Sc from neonatal (5- and 9-day-old) and prepubertal (12- and 19-day-old) rat testes and compared the status of FSH receptor (FSH-R) and androgen receptor (AR) signaling. Protein and mRNA levels of FSH-R and AR remained uniform in cultured Sc from all age groups. Androgen binding ability of AR was similar, and T-induced nuclear localization of AR was discernible in Sc from all age groups. Binding of FSH to FSH-R, subsequent production of cAMP, and mRNA of stem cell factor (SCF) and glial cell line-derived neurotrophic factor (GDNF), known to be essential for the robust differentiation of repopulating spermatogonia, were significantly augmented in prepubertal Sc compared with those in neonatal Sc. However, treatment of neonatal Sc with cholera toxin or forskolin, which stimulate cAMP production bypassing FSH-R, demonstrated a concomitant rise in SCF and GDNF mRNA expression, which was similar to the FSH-mediated rise observed in prepubertal Sc. These observations suggested that, during prepubertal Sc maturation, the ability of FSH-R to respond to FSH is significantly augmented and is associated with the robust differentiation of repopulating spermatogonia, and such a switch in Sc from FSH-resistant to FSH-responsive mode during prepubertal development may underlie the initiation of robust spermatogenesis.
FSH 和睾酮（T）通过睾丸支持细胞（Sc）调节精子发生，这些细胞具有这些激素的受体。尽管产后循环中 FSH 和 T 的水平充足，但在大鼠睾丸中，直到产后第 11 天和第 18 天才能明显观察到精原细胞 B 和精母细胞的出现。为了探讨潜在的原因，我们培养了来自新生（5 天和 9 天龄）和青春期前（12 天和 19 天龄）大鼠睾丸的 Sc，并比较了 FSH 受体（FSH-R）和雄激素受体（AR）信号的状态。来自所有年龄组的培养 Sc 中的 FSH-R 和 AR 的蛋白和 mRNA 水平保持一致。AR 的雄激素结合能力相似，并且在所有年龄组的 Sc 中都可以识别 T 诱导的 AR 核定位。已知 FSH 与 FSH-R 的结合、随后 cAMP 的产生以及干细胞因子（SCF）和胶质细胞系衍生的神经营养因子（GDNF）的 mRNA，对于再生精原细胞的强烈分化是必不可少的，在青春期前的 Sc 中比在新生的 Sc 中显著增加。然而，用霍乱毒素或 forskolin（可绕过 FSH-R 刺激 cAMP 产生）处理新生 Sc，可导致 SCF 和 GDNF mRNA 表达同时升高，与青春期前 Sc 中观察到的 FSH 介导的升高相似。这些观察结果表明，在青春期前 Sc 成熟过程中，FSH-R 对 FSH 的反应能力显著增强，与再生精原细胞的强烈分化有关，而 Sc 从青春期前发育过程中的 FSH 抵抗到 FSH 反应模式的这种转变可能是启动强烈精子发生的基础。
