Comparison of 7a-methyl-19-nortestosterone effectiveness alone or combined with progestins on androgen receptor mediated-transactivation
Por:
García-Becerra R., Ordaz-Rosado D., Noé G., Chávez B., Cooney A.J., Larrea F.
Publicada:
1 ene 2012
Resumen:
7a-methyl-19-nortestosterone (MENT) is an androgen with potent gonadotropin inhibitory activity and prostate-sparing effects. These attributes give MENT advantages over testosterone as a male contraceptive, but, as in the case of testosterone, a partial dose-dependent suppression of spermatogenesis has been observed. Combination of testosterone or MENT with synthetic progestins improves the rate of azoospermia; however, it is unknown whether these combinations affect hormone androgenicity or exert synergistic effects via progestational or androgenic interaction. Herein, using transactivation assays, we examined the ability of MENT alone or combined with several 19-nor-derived synthetic progestins to activate androgen receptor (AR)-dependent gene transcription. In addition, the capability of 7a-methyl-estradiol (7a-methyl-E 2), an aromatized metabolite of MENT, to transactivate gene transcription via estrogen receptor a (ERa; ESR1) or ERß (ESR2) was also investigated. As expected, MENT induced gene transactivation through either the progesterone receptor (PGR) or the AR. MENT was as efficient as progesterone in activating PGR-mediated reporter gene expression, but it was ten times more potent than testosterone and dihydrotestoterone in activating of AR-driven gene expression. The addition of increasing concentrations of other 19-nortestosterone derivatives (norethisterone or levonorgestrel) did not affect, in a significant manner, the ability of MENT to activate AR-dependent reporter gene transcription. The same results were obtained with different cell lines. 7a-Methyl-E 2 resulted in potent estrogen activity via both ER subtypes with efficiency similar to natural E 2. These results suggest that the addition of 19-nortestosterone-derived progestins, as a hormonal adjuvant in male fertility strategies for effective spermatogenic suppression, does not display any detrimental effect that would interfere with MENTandrogenic transcriptional activity. © 2012 Society for Reproduction and Fertility.
Filiaciones:
García-Becerra R.:
Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas Y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Mexico City 14000, Mexico
Ordaz-Rosado D.:
Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas Y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Mexico City 14000, Mexico
Noé G.:
Instituto Chileno de Medicina Reproductiva, José Victorino Lastarria 29, Santiago, Chile
Chávez B.:
Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas Y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Mexico City 14000, Mexico
Cooney A.J.:
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, United States
Larrea F.:
Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas Y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Mexico City 14000, Mexico
Bronze
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