Porter Karen L, Shetty Gunapala, Shuttlesworth Gladis A, Weng Connie C Y, Huhtaniemi Ilpo, Pakarinen Pirjo, Meistrich Marvin L
Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
J Androl. 2009 Jul-Aug;30(4):440-51. doi: 10.2164/jandrol.108.006635. Epub 2009 Jan 8.
Irradiation of LBNF(1) rat testes induces spermatogonial differentiation arrest, which can be reversed by gonadotropin-releasing hormone (GnRH) antagonist-induced suppression of intratesticular testosterone (ITT) and follicle-stimulating hormone (FSH). Although exogenous estrogen treatment also enhanced spermatogenic recovery, as measured by the tubule differentiation index (TDI), it was not clear whether estrogen stimulated spermatogonial differentiation only by further suppressing ITT or by an additional independent mechanism as well. To resolve this question, we performed the following experiments. At 15 weeks after irradiation, rats were treated with GnRH antagonist; some also received 17beta-estradiol (E2) and were killed 4 weeks later. GnRH antagonist treatment increased the TDI from 0% to 8%, and addition of E2 further increased the TDI to 39%. However, E2 addition further reduced ITT from 7 ng/g testis, observed with GnRH antagonist to 3 ng/g testis, so decreased ITT levels might have contributed to recovery. Next GnRH antagonist-treated rats were given exogenous testosterone and flutamide to stabilize ITT levels and block its action. This increased TDI slightly from 8% to 13%, but the further addition of E2 significantly raised the TDI to 27%, indicating it acted by a mechanism independent of ITT levels. Plots of TDI for all treatment groups compared with ITT, FSH, or a linear combination of ITT and FSH showed that treatments including E2 produced higher TDI values than did treatments without E2. These results indicate that there was an effect of E2 on spermatogonial differentiation because of an additional direct action on the testis that is unrelated to its suppression of testosterone or gonadotropins.
对LBNF(1)大鼠睾丸进行照射会导致精原细胞分化停滞，而促性腺激素释放激素（GnRH）拮抗剂诱导的睾丸内睾酮（ITT）和促卵泡激素（FSH）抑制可逆转这种停滞。尽管通过小管分化指数（TDI）测量，外源性雌激素治疗也能增强生精恢复，但尚不清楚雌激素是否仅通过进一步抑制ITT来刺激精原细胞分化，还是也通过额外的独立机制。为了解决这个问题，我们进行了以下实验。照射后15周，对大鼠进行GnRH拮抗剂治疗；一些大鼠还接受了17β-雌二醇（E2），并在4周后处死。GnRH拮抗剂治疗使TDI从0%增加到8%，添加E2后TDI进一步增加到39%。然而，添加E2使ITT从GnRH拮抗剂治疗时观察到的7 ng/g睾丸进一步降至3 ng/g睾丸，因此ITT水平降低可能有助于恢复。接下来，对接受GnRH拮抗剂治疗的大鼠给予外源性睾酮和氟他胺以稳定ITT水平并阻断其作用。这使TDI略有增加，从8%升至13%，但进一步添加E2显著将TDI提高到27%，表明其作用机制独立于ITT水平。所有治疗组的TDI与ITT、FSH或ITT和FSH的线性组合的对比图显示，包含E2的治疗产生的TDI值高于不包含E2的治疗。这些结果表明，E2对精原细胞分化有影响，这是由于其对睾丸有额外的直接作用，与抑制睾酮或促性腺激素无关。
