title: Effects of medroxyprogesterone and estradiol on the recovery of spermatogenesis in irradiated rats.
abstract: Suppression of intratesticular testosterone (ITT) levels is required for spermatogenic recovery in rats after irradiation, but maintenance of peripheral testosterone (T) levels is important for many male functions. Considering the preservation of peripheral T while suppressing ITT, we tested the effects of a combination of a progestin, medroxyprogesterone acetate (MPA), plus T on spermatogenic recovery after irradiation, and compared its effects to those of T alone or T combined with estradiol (E2). Rats were given testicular irradiation (6 Gy) and treated during wk 3-7 after irradiation with MPA + T, or the individual steroids with or without GnRH antagonist (GnRH-ant), or GnRH-ant alone, or T + E2. Whereas GnRH-ant alone stimulated differentiation in 55% of tubules 13 wk after irradiation compared with 0% in irradiated-only rats, the addition of MPA reduced the percentage of tubules showing differentiation to 18%. However, T or MPA alone or the combination of the two induced germ cell differentiation in only 2-4% of tubules. In contrast, E2 stimulated differentiation in 88% of tubules, and T combined with E2 still resulted in differentiation in 30% of tubules. Although both MPA and E2 suppressed ITT levels to approximately 2% of control (2 ng/g testis), MPA was a less effective stimulator of spermatogenic recovery than E2 or GnRH-ant alone. MPA's function as a weak androgen was likely responsible for inhibiting spermatogenic recovery, as was the case for all other tested androgens. Thus, for clinical protection or restoration of spermatogenesis after radiation or chemotherapy by suppressing T production, MPA, at least in the doses used in the present study, is suboptimal. The combination of an estrogen with T appears to be most effective for stimulating such recovery.
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. sgunapal@mdanderson.org.
authors.forename: Gunapala
authors.initials: G
authors.lastname: Shetty
authors.forename: Connie C Y
authors.initials: CC
authors.lastname: Weng
authors.forename: Olga U
authors.initials: OU
authors.lastname: Bolden-Tiller
authors.forename: Ilpo
authors.initials: I
authors.lastname: Huhtaniemi
authors.forename: David J
authors.initials: DJ
authors.lastname: Handelsman
authors.forename: Marvin L
authors.initials: ML
authors.lastname: Meistrich
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004338:Drug Combinations; D004958:Estradiol / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D006728:Hormones / Q000097:blood; D008297:Male; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013091:Spermatogenesis / Q000187:drug effects*; D013093:Spermatogonia / Q000166:cytology; D013737:Testis / Q000528:radiation effects*; D013739:Testosterone / Q000494:pharmacology
chemical_list: D004338:Drug Combinations; D006728:Hormones; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; D017258:Medroxyprogesterone Acetate