Anti-Müllerian hormone produces endocrine sex reversal of fetal ovaries.

We have previously reported that anti-Müllerian hormone (AMH), also known as Müllerian-inhibiting substance, the testicular glycoprotein involved in regression of the Müllerian ducts of the male fetus, induces the formation of seminiferous cord-like structures in fetal ovaries exposed to it in organ culture. We have now investigated the effect of bovine AMH, purified to homogeneity, on ovarian endocrine differentiation. Ovine fetal ovaries exposed to AMH release testosterone instead of estradiol, an endocrine sex reversal due to suppression of aromatase activity. AMH dramatically decreases the conversion rate of testosterone to estradiol and also decreases total aromatase activity, as measured by the tritiated water technique. AMH acts by decreasing aromatase biosynthesis rather than by blocking enzyme activity, as suggested by the relatively long period of AMH exposure required to produce an effect. In the rabbit fetal ovary, aromatase activity is AMH-responsive during the whole gestational period. The basal steroidogenic activity of rat fetal ovaries is extremely low but can be markedly increased by cAMP. AMH completely blocks the effect of cAMP. Taken together, our results suggest that AMH plays a pivotal role in both morphological and endocrine gonadal sex differentiation.

Anti-müllerian hormone and freemartinism: inhibition of germ cell development and induction of seminiferous cord-like structures in rat fetal ovaries exposed in vitro to purified bovine AMH.

In 13 and 14-day old fetal rat ovaries maintained 3 to 10 days in organ culture, purified bovine anti-Müllerian hormone (AMH) (1.5 to 3 micrograms/ml) induced a characteristic freemartin effect. Gonadal volume and germ cell number were significantly reduced, compared to control ovaries cultured in anhormonal medium, and epithelial cells with large clear cytoplasm linked by interdigitations differentiated in the gonadal blastema. These cells resembling rat fetal Sertoli cells became polarized and formed seminiferous cord-like structures delineated by a basal membrane containing laminin and fibronectin as is the case of testicular seminiferous cords at the first step of their differentiation. These data indicate that AMH is probably the testicular factor responsible for the morphological modifications of bovine freemartin gonads and suggest that this hormone could also be involved in normal morphological differentiation of the testis. In contrast, in fetal rat ovaries, AMH did not trigger the testosterone production which occurs in freemartin gonads at an early stage of the gestation.