Importance of the Androgen Receptor Signaling in Gene Transactivation and Transrepression for Pubertal Maturation of the Testis

Abstract

Androgens are key for pubertal development of the mammalian testis, a phenomenon that is tightly linked to Sertoli cell maturation. In this review, we discuss how androgen signaling affects Sertoli cell function and morphology by concomitantly inhibiting some processes and promoting others that contribute jointly to the completion of spermatogenesis. We focus on the molecular mechanisms that underlie anti-Müllerian hormone (AMH) inhibition by androgens at puberty, as well as on the role androgens have on Sertoli cell tight junction formation and maintenance and, consequently, on its effect on proper germ cell differentiation and meiotic onset during spermatogenesis.

Hypogonadism and Cryptorchidism

“…When boys enter puberty, the increased testosterone production causes high intratesticular testosterone levels, which strongly inhibit AMH production and overcome the stimulatory effect of FSH (55), hence resulting in a low AMH level. This effect persists until adulthood (62). Therefore, serum AMH is a biomarker of immature Sertoli cell function during prepuberty (62).…”

“…AMH level is high in the fetus, remains rather stable until birth, and is elevated during mini-puberty (60,61) due to FSH surge. Although testosterone level is also high at this time, lack of androgen receptor (AR) expression renders Sertoli cells unresponsive to the inhibitory effect of testosterone (62). During prepuberty, Sertoli cells continue producing high levels of AMH, even without FSH stimulation, because there is no strong inhibitory effect on AMH production by testosterone which is nearly absent (62).…”

“…Although testosterone level is also high at this time, lack of androgen receptor (AR) expression renders Sertoli cells unresponsive to the inhibitory effect of testosterone (62). During prepuberty, Sertoli cells continue producing high levels of AMH, even without FSH stimulation, because there is no strong inhibitory effect on AMH production by testosterone which is nearly absent (62). Sertoli cells start to express AR in the prepubertal testis (62).…”

“…During prepuberty, Sertoli cells continue producing high levels of AMH, even without FSH stimulation, because there is no strong inhibitory effect on AMH production by testosterone which is nearly absent (62). Sertoli cells start to express AR in the prepubertal testis (62). When boys enter puberty, the increased testosterone production causes high intratesticular testosterone levels, which strongly inhibit AMH production and overcome the stimulatory effect of FSH (55), hence resulting in a low AMH level.…”

“…This effect persists until adulthood (62). Therefore, serum AMH is a biomarker of immature Sertoli cell function during prepuberty (62). In humans, the presence of androgen receptors in Sertoli cells is necessary for the downregulation of AMH expression (63).…”