Shetty Gunapala, Weng Connie C Y, Meachem Sarah J, Bolden-Tiller Olga U, Zhang Zhen, Pakarinen Pirjo, Huhtaniemi Ilpo, Meistrich Marvin L
Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Endocrinology. 2006 Jan;147(1):472-82. doi: 10.1210/en.2005-0984. Epub 2005 Oct 6.
Simultaneous suppression of both testosterone and FSH with GnRH antagonists (GnRH-ant) reverses the radiation-induced block in spermatogonial differentiation in F1 hybrids of Lewis and Brown-Norway rats. Although addition of exogenous testosterone restores the block, it also raises FSH, and hence it had not been possible to conclusively determine which hormone was inhibiting spermatogonial differentiation. In the present study, we establish the relative roles of testosterone and FSH in this inhibition using three different approaches. The first approach involved the treatment of irradiated rats, in which differentiation was stimulated by GnRH-ant plus flutamide, with FSH for 2 wk; the FSH reduced the percentage of tubules that were differentiated (TDI) by about 2-fold, indicating that FSH does have an inhibitory role. The second approach involved treatment of irradiated, hypophysectomized rats with exogenous testosterone for 10 wk; testosterone also reduced the TDI, demonstrating that testosterone had a definite inhibitory effect, independent of pituitary hormones. Furthermore, in this protocol we showed that TDI in the hypophysectomized testosterone-treated group, which had higher intratesticular testosterone levels but lacked FSH, was slightly higher than the TDI in a GnRH-antagonist-testosterone-treated group of irradiated rats, which had normal physiological levels of FSH; this result supports a role for endogenous FSH in suppressing spermatogonial differentiation in the latter group. The third approach involved injection of an active anti-FSH antibody for 10 d in untreated, GnRH-ant plus flutamide-treated, or GnRH-ant plus testosterone-treated irradiated rats. This was not sufficient to increase the TDI. However, flutamide given in a similar treatment schedule did increase the TDI in GnRH-ant plus testosterone-treated rats. We conclude that both testosterone and FSH individually inhibit spermatogonial differentiation after irradiation, but testosterone is a more highly potent inhibitor than is FSH.
使用促性腺激素释放激素拮抗剂（GnRH-ant）同时抑制睾酮和促卵泡激素（FSH），可逆转辐射诱导的Lewis大鼠和Brown-Norway大鼠F1杂种精原细胞分化阻滞。尽管添加外源性睾酮可恢复这种阻滞，但它也会升高FSH，因此无法最终确定是哪种激素抑制了精原细胞分化。在本研究中，我们使用三种不同方法确定了睾酮和FSH在这种抑制作用中的相对作用。第一种方法是对经辐射的大鼠进行治疗，在这些大鼠中，GnRH-ant加氟他胺刺激分化，然后用FSH治疗2周；FSH使分化的小管百分比（TDI）降低了约2倍，表明FSH确实具有抑制作用。第二种方法是用外源性睾酮对经辐射、垂体切除的大鼠进行10周治疗；睾酮也降低了TDI，表明睾酮具有明确的抑制作用，与垂体激素无关。此外，在该方案中我们发现，垂体切除的睾酮治疗组中，睾丸内睾酮水平较高但缺乏FSH，其TDI略高于经辐射的GnRH拮抗剂-睾酮治疗组（该组FSH水平正常）的TDI；这一结果支持内源性FSH在抑制后一组精原细胞分化中发挥作用。第三种方法是在未治疗的、GnRH-ant加氟他胺治疗的或GnRH-ant加睾酮治疗的经辐射大鼠中注射活性抗FSH抗体10天。这不足以增加TDI。然而，在类似治疗方案中给予氟他胺确实增加了GnRH-ant加睾酮治疗大鼠的TDI。我们得出结论，辐射后睾酮和FSH均可单独抑制精原细胞分化，但睾酮是比FSH更强效的抑制剂。
