Epitestosterone- and testosterone-replacement in immature castrated rats changes main testicular developmental characteristics

Epitestosterone is the 17α-epimer of testosterone and has been described as an anti-androgen, since it inhibits the effects produced by testosterone and dihydrotestosterone via the nuclear androgen receptor (nAR). However, epitestosterone also displays an effect which is similar to the non-classical...

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Published in:	Molecular and cellular endocrinology Vol. 461; pp. 112 - 121
Main Authors:	Cavalari, Fernanda Carvalho, da Rosa, Luciana Abreu, Escott, Gustavo Monteiro, Dourado, Tadeu, de Castro, Alexandre Luz, Kohek, Maria Beatriz da Fonte, Ribeiro, Maria Flávia Marques, Partata, Wania Aparecida, de Fraga, Luciano Stürmer, Loss, Eloísa da Silveira
Format:	Journal Article
Language:	English
Published:	Ireland Elsevier B.V 05-02-2018
Subjects:	Androgens Animals Castration Cetrorelix Electrophysiological response Epitestosterone - pharmacology Gene Expression Regulation, Developmental - drug effects Genital development Gonadotropin-Releasing Hormone - analogs & derivatives Gonadotropin-Releasing Hormone - antagonists & inhibitors Gonadotropin-Releasing Hormone - metabolism Gonadotropin-Releasing Hormone - pharmacology Hormone Replacement Therapy Male Membrane Potentials - drug effects Nuclear androgen receptor Rats, Wistar Receptors, Androgen - genetics Receptors, Androgen - metabolism Seminiferous Tubules - drug effects Seminiferous Tubules - metabolism Sertoli cells Sertoli Cells - drug effects Sertoli Cells - metabolism Testis - drug effects Testis - growth & development Testosterone - pharmacology Androgens Genital development Electrophysiological response Nuclear androgen receptor Sertoli cells Cetrorelix
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Summary:	Epitestosterone is the 17α-epimer of testosterone and has been described as an anti-androgen, since it inhibits the effects produced by testosterone and dihydrotestosterone via the nuclear androgen receptor (nAR). However, epitestosterone also displays an effect which is similar to the non-classical effect of testosterone, depolarizing the membrane potential of Sertoli cells and inducing a rapid Ca2+ uptake. This study aimed to investigate the effects of a treatment with epitestosterone on developmental parameters of immature rats. Animals were chemically castrated by using the gonadotropin-releasing hormone (GnRH) antagonist cetrorelix and then received a replacement of 7 days with epitestosterone or testosterone. Replacement with either epitestosterone or testosterone restored the anogenital distance (AGD) and testicular weight which had been reduced by chemical castration. The immunocontent of nAR and the nAR-immunoreactivity were reduced by epitestosterone treatment in the testis of both castrated and non-castrated animals. Furthermore, testosterone was unable of changing the membrane potential of Sertoli cells through its non-classical action in the group of animals castrated and replaced with epitestosterone. In conclusion, in relation to the level of protein expression of nAR epitestosterone acts as an anti-androgen. However, it acts in the same way as testosterone when genital development parameters are evaluated. Moreover, in castrated rats epitestosterone suppressed the non-classical response of testosterone, changing the pattern of testosterone signalling via a membrane mechanism in Sertoli cells. •Testosterone and epitestosterone recovered genital development in castrated rats.•Epitestosterone reduces intracellular androgen receptor expression in castrated rats.•Androgen rapid signalling is altered by cetrorelix plus epitestosterone treatment.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0303-7207 1872-8057
DOI:	10.1016/j.mce.2017.08.023