Inhibition of recovery of spermatogenesis in irradiated rats by different androgens.
We previously showed that exogenous testosterone (T) inhibited GnRH-antagonist-stimulated spermatogenic recovery in irradiated rats through an androgen-receptor-mediated action. In the present study, we tested whether the inhibition is attributable to T, a specific androgenic metabolite of T, or a general property of androgens in this system. In addition, we also tested whether estradiol-17beta (E2), a metabolite of T, is similarly inhibitory. Rats irradiated with 5 Gy were treated with a GnRH antagonist during wk 3-7. Neither irradiation nor GnRH-antagonist treatment produced biologically significant changes in the relative intratesticular levels of several androgenic metabolites. Next, groups of rats, irradiated and treated with GnRH antagonist as above, were given various doses of one of the following androgens: T, 5alpha-dihydrotestosterone, 7alpha-methyl-19-nortestosterone, methyltrienolone, or E2. The percentage of tubules showing differentiation (tubule differentiation index) was increased to 68% by the GnRH antagonist, from a value of 0.1% in irradiated-only rats at 13 wk after irradiation. All of the added androgens inhibited spermatogenic recovery, lowering the tubule differentiation index to between 0.4-36%, but no inhibition was observed with the addition of E2. Of all the androgen treatments tested, T (given as daily injections of T propionate) minimally inhibited spermatogenic recovery while maintaining androgen-responsive tissue weights, and might be most useful in clinical studies. Hormonal measurements in androgen-treated rats were most consistent with the androgen inhibition of spermatogenic recovery in irradiated rats being a combined result of a direct inhibitory effect of all androgens on the testis and an indirect effect through the pituitary by raising levels of FSH, which seems to add to the inhibition of spermatogenic recovery.
Shetty
Gunapala
G
Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. gshetty@audumla.mdacc.tmc.edu
Wilson
Gene
G
Hardy
Matthew P
MP
Niu
Enmei
E
Huhtaniemi
Ilpo
I
Meistrich
Marvin L
ML
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003037:Cobalt Radioisotopes; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005640:Follicle Stimulating Hormone / Q000097:blood; D005837:Genitalia, Male / Q000033:anatomy & histology; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013091:Spermatogenesis / Q000187:drug effects* / Q000528:radiation effects*; D013094:Spermatozoa / Q000187:drug effects / Q000528:radiation effects; D013737:Testis / Q000033:anatomy & histology / Q000737:chemistry; D013739:Testosterone / Q000032:analysis / Q000494:pharmacology
D000728:Androgens; D003037:Cobalt Radioisotopes; D004963:Estrenes; D013196:Dihydrotestosterone; D015741:Metribolone; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; C073330:methylestrenolone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C062876:cetrorelix