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Inhibition of Recovery of Spermatogenesis in Irradiated Rats by Different Androgens

Department of Experimental Radiation Oncology (G.S., G.W., M.L.M.), The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030; Department of Physiology (I.H.), University of Turku, 20520 Turku, Finland; and Center for Biomedical Research (M.P.H., E.N.), The Population Council, New York, New York 10021

Address all correspondence and requests for reprints to: Gunapala Shetty, Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030. E-mail: gshetty{at}audumla.mdacc.tmc.edu.

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-17ß (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, 5-dihydrotestosterone, 7-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.

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