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

OBJECTIVE: 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.
DESIGN: Experimental study.
SETTING: Academic medical center for reproductive science. PATIENT(S): The hGL cells were obtained from consenting patients undergoing IVF treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): 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. RESULT(S): 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. CONCLUSION(S): The AMH acts through AMHR2 to inhibit FSH-induced adenylyl cyclase activation, aromatase expression, and E2 production.