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Role of non-classical effects of testosterone and epitestosterone on AMH balance and testicular development parameters

da Rosa LA, Escott GM, Simonetti RB, da Silva JCD, Werlang ICR, Goldani MZ, de Fraga LS, Loss EDS

Molecular and cellular endocrinology, 2020

Abstract

Testosterone (T) and its 17-α epimer, epitestosterone (EpiT), are described as having non-classical effects in addition to their classical androgen actions via the intracellular androgen receptor (iAR). The actions of these androgens play an essential role in triggering factors that shift Sertoli cells from the proliferation phase to the maturation phase. This process is essential for successful spermatogenesis and normal fertility. The aim of this work was to investigate the difference between T and EpiT effects in normal and in chemically castrated Wistar rats. We also tested the effects of these hormones when the iAR-dependent pathways were inhibited by the antiandrogen flutamide. Rats were chemically castrated on postnatal day (pnd) 5 using EDS, a cytotoxic agent that promotes apoptosis of Leydig cells, reducing androgen levels. Then, animals received replacement with T or EpiT and were treated or not with flutamide from pnd 6 to pnd 13 or 20 and were euthanized on pnd 14 and 21. Animals treated with EpiT and flutamide had lower body weight overall. Epididymis weight was also reduced in animals treated with EpiT and flutamide. Flutamide per se reduced epididymis weight at both ages (pnd 14 and 21). Testicular weight and the testicular/body weight ratio were reduced in EDS animals, and flutamide further reduced this weight in animals which received T replacement. EDS administration reduced mRNA levels of both AMH (anti-Müllerian hormone) and its receptor, AMHR2, at pnd…

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