COMPARISON OF THE RESPONSE OF RAT TESTIS AND ACCESSORY SEX-ORGANS TO TREATMENT WITH TESTOSTERONE AND THE SYNTHETIC ANDROGEN METHYLTRIENOLONE (R1881)

We have studied the ability of the synthetic androgen methyltrienolone (R1881) to maintain testis and accessory organ weights, as compared t o the effect of testosterone propionate (TP). In contrast to TP, R1881 is not metabolized and does not significantly bind to androgen-bindin g protein (ABP). Thirty-six rats were treated with ethane dimethane su lphonate (EDS) and GnRH antagonist (Org30267) to abolish all testicula r androgen production, and recombinant human FSH (rec-hFSH, Org32489) was administered to ensure adequate FSH levels. Of these rats, five gr oups of four rats were treated daily with 0-, 50-, 100-, 200-, and 400 -mu g TP, s.c., and four groups of four rats were treated daily with 1 50-, 300-, 600-, and 1200-mu g R1881, s.c. One control group of four r ats received vehicle injections only. EDS treatment, followed by GnRH antagonist and rec-hFSH treatment for 17 days, significantly reduced t estis, prostate, and seminal vesicle weights (P < 0.001, P < 0.01, P < 0.001, respectively). Simultaneous treatment with androgens prevented this organ weight decrease, in a dose-dependent manner. In all TP-tre ated animals, relative weights (% of control) of the accessory sex org ans were significantly higher than the relative testis weights (P < 0. 001). However, there was no difference in relative weights between tes tis and accessory sex organs in the R1881-treated animals. In another series of experiments, we investigated the effect of treatment with Fi nasteride, a 5 alpha-reductase inhibitor, on testis and accessory sex organ weights in rats treated with EDS and TP, Treatment with EDS, TP (300 mu g/day) and Finasteride (40 mg/kg/day) did not alter testis wei ght as compared to the effect of treatment with EDS and TP alone. Pros tate and seminal vesicle weights were, however, markedly reduced (sign ificantly different from rats treated with EDS and TP alone; P < 0.01 and P < 0.05, respectively). Immunohistochemical analysis of androgen- receptor (AR) expression in the testis revealed that testicular AR imm unoexpression is androgen dependent and that FSH alone is not able to maintain AR immunoexpression. Furthermore, the stage-dependent pattern of AR immunoexpression in Sertoli-cell nuclei, during the spermatogen ic cycle, is identical in all TP- and R1881-treated rats. It is conclu ded that testes, prostate, and seminal vesicles are equally stimulated when the androgen receptor in these tissues is exposed to the same in tracellular concentration of free androgen and that the low 5 alpha-re ductase activity in the testis plays a critical role in the differenti al response of the testis and the accessory sex organs to T. Furthermo re, stage-dependent AR immunoexpression in Sertoli cells does occur in the absence of testicular androgen production and is not due to andro gen metabolism or local differences in androgen concentration.