Antimüllerian hormone inhibits follicle-stimulating hormone-induced adenylyl cyclase activation, aromatase expression, and estradiol production in human granulosa-lutein cells

Abstract

To investigate the effects of antimüllerian hormone (AMH) on basal and FSH-induced cytochrome P450 aromatase (aromatase) expression and E2 production in human granulosa-lutein (hGL) cells, and to elucidate the mechanism by which AMH exerts its effects. Experimental study. Academic medical center for reproductive science. The hGL cells were obtained from consenting patients undergoing IVF treatment. None. Primary cultures of hGL cells were used to examine the effects of AMH (10 ng/mL) on basal and FSH (0.2 IU/mL)-stimulated E2 and intracellular cyclic adenosine 3':5' monophosphate (cAMP) accumulation, as well as aromatase and FSH receptor expression. Small interfering RNA targeting type II AMH receptor (AMHR2) was used to verify the specificity of the effects. Treatment with AMH significantly reduced FSH-stimulated aromatase expression and E2 accumulation, whereas it had no measurable effects on basal and/or 8-Br-cAMP-stimulated levels. The FSH receptor messenger RNA and protein levels were not altered in AMH-treated cells. Cotreatment with AMH suppressed FSH-induced increases in intracellular cAMP. Knockdown of AMHR2 reversed the effects of AMH on aromatase expression. The AMH acts through AMHR2 to inhibit FSH-induced adenylyl cyclase activation, aromatase expression, and E2 production.