AMH inhibits androgen production in human theca cells

Both excessive ovarian production of AMH and androgen are important features of polycystic ovary syndrome (PCOS). Present study aimed to explore the direct effect of AMH on androgen production in human theca cells. Primary cultured human theca cells were treated with AMH, an ALK2 (the BMP type 1 receptor) inhibitor and an ALK5 (the TGFβ type 1 receptor) inhibitor. AMH significantly suppresses the expression of the androgen synthesis-related enzyme CYP17A1 and reduces the production of androstenedione and testosterone in normal human theca cells and PCOS theca cells. Inhibitors of ALK2/3 and ALK5 antagonize the effect of AMH on the expression of CYP17A1 . Although both ALK5 and ALK2 interact with AMHR2 in the presence of AMH, AMH activated neither TGFβR-Smads (Smad 2/3) nor BMP R-Smads (Smad 1/5/8). Our data suggested that AMH suppresses androgen synthesis-related enzyme CYP17A1 expression and inhibits androgen production in human theca cells, which process may be mediated by ALK2 and ALK5. • AMH suppresses CYP17A1 expression in normal human theca cells and PCOS theca cells. • AMH reduces the androgen production in normal human theca cells and PCOS theca cells. • ALK2 and ALK5 interact with AMHR2 in the presence of AMH in human theca cells. • ALK2 and ALK5 may mediate the regulation of androgen production by AMH in theca cells.