Molecular mechanisms underlying AMH elevation in hyperoestrogenic states in males

Abstract

Anti-Müllerian hormone (AMH) is secreted by Sertoli cells of the testes from early fetal life until puberty, when it is downregulated by androgens. In conditions like complete androgen insensitivity syndrome (CAIS), AMH downregulation does not occur and AMH increases at puberty, due in part to follicle-stimulating hormone (FSH) effect. However, other conditions like Peutz-Jeghers syndrome (PJS), characterised by low FSH, also have increased AMH. Because both CAIS and PJS may present as hyperoestrogenic states, we tested the hypothesis that oestradiol (E2) upregulates AMH expression in peripubertal Sertoli cells and explored the molecular mechanisms potentially involved. The results showed that E2 is capable of inducing an upregulation of endogenous AMH and of the AMH promoter activity in the prepubertal Sertoli cell line SMAT1, signalling through ERα binding to a specific ERE sequence present on the hAMH promoter. A modest action was also mediated through the membrane oestrogen receptor GPER. Additionally, the existence of ERα expression in Sertoli cells in patients with CAIS was confirmed by immunohistochemistry. The evidence presented here provides biological plausibility to the hypothesis that testicular AMH production increases in clinical conditions in response to elevated oestrogen levels.

DYRK1A Overexpression in Mice Downregulates the Gonadotropic Axis and Disturbs Early Stages of Spermatogenesis

“…Furthermore (Figure 4a), the hormone assay data revealed hypogonadotropic hypogonadism in Tg mice, with low plasma FSH, LH, and testosterone levels and an elevated plasma AMH level. This situation has been reported in other disorders, such as delayed puberty (i.e., childhood levels or hormones) and central hypogonadism (high AMH levels for age) [29][30][31]. AMH is secreted by prepubertal Sertoli cells in response to Furthermore (Figure 4a), the hormone assay data revealed hypogonadotropic hypogonadism in Tg mice, with low plasma FSH, LH, and testosterone levels and an elevated plasma AMH level.…”

“…AMH is secreted by prepubertal Sertoli cells in response to Furthermore (Figure 4a), the hormone assay data revealed hypogonadotropic hypogonadism in Tg mice, with low plasma FSH, LH, and testosterone levels and an elevated plasma AMH level. This situation has been reported in other disorders, such as delayed puberty (i.e., childhood levels or hormones) and central hypogonadism (high AMH levels for age) [29][30][31]. AMH is secreted by prepubertal Sertoli cells in response to FSH, and AMH levels are elevated during fetal life and throughout puberty.…”

Elevated Anti-Müllerian Hormone Levels in Newborns of Women with Polycystic Ovary Syndrome: a Systematic Review and Meta-analysis Based on Observational Studies

“…In the male fetus, AMH was secreted by Sertoli cells of the testes from early fetal life, which remained a high level and thus induced physiological involution of the paramesonephric Müllerian ducts. Although the regression of the paramesonephric Müllerian ducts was complicated early in gestation, the production process of AMH by Sertoli cells continued until adulthood [ 42 ]. In the female fetus, the AMH was secreted by granulosa cells of the ovarian follicles from 36 weeks of gestation until menopause, whose expression peak was in preantral follicles and small antral follicles.…”

Clinical Utility of Anti-Mullerian Hormone in Pediatrics

“…In androgen insensitivity syndrome, however, the relatively high gonadotropins and lack of a functional androgen receptor cause AMH levels to be inappropriately high for the degree of testosterone in the serum ( 56 ). Recent studies indicate that the hyperestrogenic state in complete AIS may also play a role in AMH elevation ( 58 ). A study of the testosterone response to human chorionic gonadotropin (hCG) stimulation in prepubertal patients with 46,XY DSD found that a normal serum AMH had a positive predictive value of 84% for a normal post-hCG testosterone level, but a low AMH was not useful in predicting a suboptimal testosterone response ( 59 ).…”