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Abstract

Inhibition of recovery of spermatogenesis in irradiated rats by different androgens 
Shetty,Gunapala; Wilson,Gene; Hardy,Matthew P.; Niu,Enmei; Huhtaniemi,Ilpo; Meistrich,Marvin L.
Endocrinology 143(9): 3385-3396
Publication date: 2002


We previously showed that exogenous testosterone (T) inhibitedGnRH-antagonist-stimulated spermatogenic recovery in irradiatedrats through an androgen-receptor-mediated action. In the presentstudy, we tested whether the inhibition is attributable to T,a specific androgenic metabolite of T, or a general propertyof androgens in this system. In addition, we also tested whetherestradiol-17ß (E2), a metabolite of T, is similarlyinhibitory. Rats irradiated with 5 Gy were treated with a GnRHantagonist during wk 3-7. Neither irradiation nor GnRH-antagonisttreatment produced biologically significant changes in the relativeintratesticular levels of several androgenic metabolites. Next,groups of rats, irradiated and treated with GnRH antagonistas above, were given various doses of one of the following androgens:T, 5-dihydrotestosterone, 7-methyl-19-nortestosterone, methyltrienolone,or E2. The percentage of tubules showing differentiation (tubuledifferentiation index) was increased to 68% by the GnRH antagonist,from a value of 0.1% in irradiated-only rats at 13 wk afterirradiation. All of the added androgens inhibited spermatogenicrecovery, lowering the tubule differentiation index to between0.4-36%, but no inhibition was observed with the additionof E2. Of all the androgen treatments tested, T (given as dailyinjections of T propionate) minimally inhibited spermatogenicrecovery while maintaining androgen-responsive tissue weights,and might be most useful in clinical studies. Hormonal measurementsin androgen-treated rats were most consistent with the androgeninhibition of spermatogenic recovery in irradiated rats beinga combined result of a direct inhibitory effect of all androgenson the testis and an indirect effect through the pituitary byraising levels of FSH, which seems to add to the inhibitionof spermatogenic recovery.