7α-methyl-19-nortestosterone (trestolone acetate) is an androgen with powerful gonadotropin-inhibiting activity and prostate protective effects. These properties make trestolone acetate superior to testosterone as a male contraceptive, but as in the case of testosterone, partial dose-dependent inhibition of spermatogenesis has been observed. The combination of testosterone or trestolone acetate with synthetic progesterone can increase the incidence of azoospermia.
However, it is unclear whether these combinations affect the androgenicity of hormones or work synergistically through progesterone or androgen interactions. Here, using trans activation analysis, we examined the ability of trestolone acetate to activate androgen receptor (AR) dependent gene transcription, either alone or in combination with several 19-nor derived synthetic progesterone. In addition, the aromatization metabolite of
Trestolone acetate 7α-methylestradiol (7α-methyl E2) was studied through the estrogen receptor α (ERα; The ability of ESR1) or ERβ (ESR2) to transactivate gene transcription. As expected, trestolone acetate induced trans-activation of genes via the progesterone receptor (PGR) or AR. trestolone acetate was as effective as progesterone in activating PGR-mediated reporter gene expression, but ten times more effective than testosterone and DHT in activating AR-driven gene expression.
The addition of 19 other nortestosterone derivatives (norethisterone or levonorgestrel) with increased concentrations did not significantly affect the ability of trestolone acetate to activate AR-dependent reporter gene transcription. The same results were obtained with different cell lines. 7α-methyl-E2 produces powerful estrogenic activity through both ER subtypes, with an efficiency similar to that of natural E2. These results suggest that the addition of 19 nortestosterone derived progesterone as a hormonal adjuvant that effectively inhibits spermatogenesis in male fertility strategies does not show any harmful effects that interfere with the transcriptional activity of trestolone acetate androgens.
However, it is unclear whether these combinations affect the androgenicity of hormones or work synergistically through progesterone or androgen interactions. Here, using trans activation analysis, we examined the ability of trestolone acetate to activate androgen receptor (AR) dependent gene transcription, either alone or in combination with several 19-nor derived synthetic progesterone. In addition, the aromatization metabolite of
Trestolone acetate 7α-methylestradiol (7α-methyl E2) was studied through the estrogen receptor α (ERα; The ability of ESR1) or ERβ (ESR2) to transactivate gene transcription. As expected, trestolone acetate induced trans-activation of genes via the progesterone receptor (PGR) or AR. trestolone acetate was as effective as progesterone in activating PGR-mediated reporter gene expression, but ten times more effective than testosterone and DHT in activating AR-driven gene expression.
The addition of 19 other nortestosterone derivatives (norethisterone or levonorgestrel) with increased concentrations did not significantly affect the ability of trestolone acetate to activate AR-dependent reporter gene transcription. The same results were obtained with different cell lines. 7α-methyl-E2 produces powerful estrogenic activity through both ER subtypes, with an efficiency similar to that of natural E2. These results suggest that the addition of 19 nortestosterone derived progesterone as a hormonal adjuvant that effectively inhibits spermatogenesis in male fertility strategies does not show any harmful effects that interfere with the transcriptional activity of trestolone acetate androgens.