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The pharmacologic effects of S -N- 4-cyanotrifluoromethyl-phenyl 3-fluoro, 4-chlorophenoxy hydroxymethyl-propanamide S were characterized in male rats as an animal model of hormonal male contraception. In castrated male rats, the ED50 of S in the prostate and levator ani muscle was 0. In intact male rats treated for up to 10 wk with S and estradiol benzoate EB; necessary to maintain sexual behavior in rats , S showed biphasic effects on androgenic tissues and spermatogenesis by suppressing serum concentrations of LH and FSH.
EB alone showed no effect on spermatogenesis. S increased bone mineral density and lean mass but reduced fat mass in a dose-dependent manner. This is the first study to show that a selective androgen receptor modulator combined with EB is an effective and reversible regimen for hormonal male contraception in rats.
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Figures Figure 1 5 Chemical structures, AR binding affinity,…. Figure 1 13 Chemical structures, AR binding affinity, and in vitro transcriptional activation of C-6 and….
Chemical structures, AR binding affinity, and in vitro transcriptional activation of C-6 and S AR binding affinity was determined using a radioligand competitive assay. The ability of compound of interest to induce AR-mediated transcriptional activation was determined using a cotransfection assay in CV-1 cells. The transcriptional activity induced by each compound at a concentration of 10 n m was reported as the percentage of that observed for 1 n m DHT.
Figure 2 5 A, The androgenic activity and…. Figure 2 13 A, The androgenic activity and anabolic activity of S in castrated male rats. A, The androgenic activity and anabolic activity of S in castrated male rats. S was administrated to animals via daily sc injections for 14 d with doses ranging from 0.
All organ weights were normalized with body weight and presented as the percentage of intact control. B, Dose-response curves of S in castrated male rats. Emax and ED 50 in this figure were obtained by nonlinear least-square regression analysis.
C, The androgenic activity and anabolic activity of S in intact male rats. ORX, Castrated. Figure 3 5 Mean plasma concentration-time profile of…. Figure 3 13 Mean plasma concentration-time profile of S in male rats.
Plasma concentrations of S…. Mean plasma concentration-time profile of S in male rats. Figure 4 5 Testicular sperm concentrations. Each bar…. Figure 4 13 Testicular sperm concentrations. Testicular sperm concentrations. Figure 5 5 The linear correlation between the…. Figure 5 13 The linear correlation between the dose rate of S and body composition percent…. The linear correlation between the dose rate of S and body composition percent of FM and percent of fat free mass.
See this image and copyright information in PMC. Similar articles A selective androgen receptor modulator for hormonal male contraception. Chen J, et al. J Pharmacol Exp Ther. Epub Sep 3. PMID: Nonsteroidal selective androgen receptor modulators enhance female sexual motivation.
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