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

Abstract

Anti-Müllerian hormone (AMH) is a distinctive biomarker of the immature Sertoli cell. AMH expression, triggered by specific transcription factors upon fetal Sertoli cells differentiation independently of gonadotropins or sex steroids, drives Müllerian duct regression in the male, preventing the development of the uterus and Fallopian tubes. AMH continues to be highly expressed by Sertoli until the onset of puberty, when it is downregulated to low adult levels. FSH increases testicular AMH output by promoting immature Sertoli cell proliferation and individual cell expression. AMH secretion also showcases a differential regulation exerted by intratesticular levels of androgens and estrogens. In the fetus and the newborn, Sertoli cells do not express the androgen receptor, and the high androgen concentrations do not affect AMH expression. Conversely, estrogens can stimulate AMH production because estrogen receptors are present in Sertoli cells and aromatase is stimulated by FSH. During childhood, sex steroids levels are very low and do not play a physiological role on AMH production. However, hyperestrogenic states upregulate AMH expression. During puberty, testosterone inhibition of AMH expression overrides stimulation by estrogens and FSH. The direct effects of sex steroids on AMH transcription are mediated by androgen receptor and estrogen receptor α action on AMH promoter sequences. A modest estrogen action is also mediated by the membrane G-coupled estrogen receptor GPER. The understanding of these complex regulatory mechanisms helps in the interpretation of serum AMH levels found in physiological or pathological conditions, which underscores the importance of serum AMH as a biomarker of intratesticular steroid concentrations.

Effects of Growth Factors on In Vitro Culture of Neonatal Piglet Testicular Tissue Fragments

“…AMH is one of the earliest cell-specific proteins produced by Sertoli cells, which starts to be expressed at the 8th week of gestation in the human or 12.5 days post-coitum in the mouse [ 65 , 66 ]. The expression of AMH in Sertoli cells is then continuously observed during the fetal and postnatal periods, and up until the onset of puberty [ 67 ]. During the pubertal period, the expression of AMH starts to progressively decrease, which coincides with the formation of the blood–testis barrier and the onset of germ cell meiosis [ 68 , 69 , 70 ].…”

Anti-Müllerian hormone, testicular descent and cryptorchidism

“…The circulating AMH levels are commensurate with the mass of functional Sertoli cells in the fetus ( 29 ), newborns ( 82 ), infants and children ( 51 , 83 ). In males of pubertal age, serum AMH is indicative of the maturation status of Sertoli cells, reflecting testosterone concentration and action within the testis ( 84 , 85 ). This is especially useful in the early stages of pubertal development, i.e.…”

Unveiling the roles of Sertoli cells lineage differentiation in reproductive development and disorders: a review

“…In addition, downregulation of Tetraspanin 8, Sostdc1, and miR-92a-3p in pubertal Sertoli cells results in is the maintenance of normal sperm quantity and quality ( 27 , 28 ). In this process, downregulation of miR-92a-3p is induced by gonadotropins, and gonadotropin promotes the proliferation of immature Sertoli cells and targets Sertoli cells to support the expansion and differentiation of pre-meiotic germ cells ( 28 – 30 ). Several theories have been proposed on the mechanism underlying the origin of Sertoli cells; however, further studies are warranted to explore their embryonic origin.…”