Early Expression of the Androgen Receptor in the Sertoli Cells of a Marsupial Coincides with Downregulation of Anti-Müllerian Hormone at the Time of Urogenital Virilization

Abstract

Anti-Müllerian hormone (AMH), responsible for the regression of Müllerian ducts, is strongly expressed by eutherian fetal and postnatal Sertoli cells. Both AMH and testosterone levels are high during the period of fetal reproductive tract virilization which occurs largely in utero in eutherian mammals. Taking advantage of the fact that differentiation of the urogenital tract occurs after birth in marsupials, we studied the ontogeny and regulation of AMH in the tammar wallaby testis and related it to the expression of the androgen receptor in Sertoli cells. Testicular AMH expression was high between days 10–30 post partum, then fell to basal levels by day 60 and remained low until day 90, the oldest age examined. AMH expression was repressed by treatment of male pouch young with the potent androgen androstanediol. Thus, in the tammar, AMH expression decreases in response to androgen at the time of initial urogenital masculinization, in contrast to the situation in humans in which AMH is repressed by testosterone only at the time of puberty. The difference might be explained by the timing of androgen receptor expression which appears in tammar Sertoli cells at around day 40 of pouch life but only at a later developmental stage in eutherians.

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

“…As previously mentioned, the decrease in AMH expression at pubertal onset is indicative of Sertoli cell maturation. Despite the fact that AMH downregulation by androgens has been established a long time ago in all animals studied, including human [55,58,96,142], mouse [8,48,49,143], ram [144,145], pig [146,147], stallion [148], bovine [149,150], and tammar wallaby [151], it has not been until recently that the underlying mechanism of androgen action was described [30].…”

AMH Regulation by Steroids in the Mammalian Testis: Underlying Mechanisms and Clinical Implications

“…Intratesticular testosterone triggers a number of morphologic and functional changes in Sertoli cells [reviewed in ref ( 18 )]. One distinctive change is the decrease in AMH production that occurs as one of the first clinical signs of pubertal development in boys ( 48 ), as well as in numerous other mammals ( 3 , 25 , 70 , 71 ), in coincidence with the onset of germ cell meiosis ( 50 ). Results obtained in experimental mouse models support these observations ( 30 ).…”