Estrogen enhances recovery from radiation-induced spermatogonial arrest in rat testes.
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.
Porter
Karen L
KL
Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. karen.porter@amedd.army.mil
Shetty
Gunapala
G
Shuttlesworth
Gladis A
GA
Weng
Connie C Y
CC
Huhtaniemi
Ilpo
I
Pakarinen
Pirjo
P
Meistrich
Marvin L
ML
D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D005485:Flutamide / Q000494:pharmacology; D005640:Follicle Stimulating Hormone / Q000097:blood; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013091:Spermatogenesis / Q000187:drug effects* / Q000528:radiation effects; D013093:Spermatogonia / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000528:radiation effects*; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000726:Androgen Antagonists; D013739:Testosterone; D004958:Estradiol; D005485:Flutamide; D005640:Follicle Stimulating Hormone