Suppression of androgen action and the induction of gross abnormalities of the reproductive tract in male rats treated neonatally with diethylstilbestrol.

摘要: This study evaluated whether androgen action is altered in rats treated neonatally with diethylstilbestrol (DES) at a dose that induced reproductive tract abnormalities. Rats were on alternate days 2-12 10 microg DES and studied Day 18. DES-induced abnormalities included 70% reduction testis weight, distension overgrowth of the rete, epithelial height efferent ducts, underdevelopment epididymal duct epithelium, vas deferens, convolution extra-epididymal vas. In DES-treated rats, receptor (AR) immunoexpression was virtually absent from all affected tissues testis, whereas AR expression controls intense stromal cells. The change confirmed by Western analysis for testis. 1 DES, or minor, except 38% weight; loss also did not occur these rats. Treatment-induced changes paralleled Leydig cell volume per (91% 10-microg group; no 1-microg group). To test suppression production alone could induce comparable to either potent gonadotropin-releasing hormone antagonist (GnRHa) flutamide (50 mg/kg/day). These treatments reduced weight (68% GnRHa, 40% flutamide), generally retarded development but failed DES. GnRHa caused detectable target tissues, exception minor testes flutamide-treated males. treatment (83%) Immunoexpression estrogen alpha (ER alpha) ducts ER beta unaffected any above treatments. Neonatal coadministration testosterone esters (TE; 200 microg) prevented most morphological alone, though still subnormal (46% + TE vs 72% 49% alone) some lumenal evident ducts. Coadministration (confirmed blot analysis). It concluded 1) neonatal male rat high (10 are associated volume; 2) largely lower (1 microg); 3) interfere (flutamide) alter as DES; 4) grossly androgen:estrogen balance (low estrogen) may underlie abnormalities, other than doses