Anti-Mullerian hormone reduces follicle sensitivity to follicle-stimulating hormone in human granulosa cells

Objective: To determine that anti-Mullerian hormone (AMH) has been shown to inhibits E-2 production in rodents and in luteinized granulosa cells (GC). We determined whether this occurs in human cells most highly expressing AMH (i.e., from small antral follicles) and whether this is an effect on aromatase promoter activity. We also investigated the effects of AMH on other factors determining FSH sensitivity. Design: Granulosa cells were exposed to AMH with and without gonadotropins for 48 hours. Setting: University laboratory. Patient(s): Not applicable. Intervention(s): None. Main Outcome Measure(s): Aromatase and FSH receptor messenger RNA expression measured using real time quantitative polymerase chain reaction (PCR). Aromatase promoter II activity measured using a luciferase assay. Estradiol, inhibin A and B, and vascular endothelial growth factor production were measured in the conditioned medium. Result(s): The AMH decreased gonadotropin-stimulated aromatase expression and decreased forskolin-stimulated aromatase in KGN cells and this effect was through a dose-dependent inhibition of promoter II. Surprisingly, AMH also reduced FSH receptor mRNA expression. High AMH doses had no effect on inhibin B, whereas a low dose stimulated production. There was no effect on inhibin A or vascular endothelial growth factor. Conclusion(s): The AMH inhibits factors affecting FSH sensitivity. As AMH levels decrease with follicle growth, this inhibition would be removed. The AMH overproduction in anovulatory polycystic ovaries (PCO) may therefore restrict folliculogenesis by an inhibitory effect on FSH sensitivity, thereby contributing to anovulation. (Fertil Steril (R) 2011; 96: 1246-51. (C) 2011 by American Society for Reproductive Medicine.)