Granulosa Cell Production of Anti-Müllerian Hormone Is Increased in Polycystic Ovaries

TLDR

Anti‑Müllerian hormone is of renewed interest for its ovarian role, though data are sparse and it appears to inhibit follicle growth. The study examined AMH production by granulosa cells from follicles of various sizes in normal ovaries versus ovulatory and anovulatory polycystic ovaries. Granulosa cells were cultured for 48 h with or without FSH or LH, and AMH was measured in follicular fluid and conditioned media, revealing low or undetectable levels in follicles >9 mm, luteinized cells, and theca/stroma. Granulosa cells from PCO ovaries produced markedly higher AMH—fourfold in ovulatory and 75‑fold in anovulatory PCOs compared to normal ovaries—and gonadotropin modulation differed, with FSH suppressing and LH enhancing AMH in PCO cells, suggesting excess AMH contributes to impaired follicle growth and ovulation in PCOS.

Abstract

There has been renewed interest in anti-Müllerian hormone (AMH) because of its role in the ovary. Data on its actions are sparse, but it appears to inhibit follicle growth. Interestingly, serum AMH is two to three times higher in women with polycystic ovary (PCO) syndrome than women with normal ovaries.We examined the production of AMH by cells from a range of follicle sizes from normal ovaries and compared this with production by ovulatory and anovulatory (anov) PCOs.Granulosa cells (GCs) and theca and follicular fluid (ff) were isolated from intact follicles. Cells were cultured for 48 h +/- FSH or LH, and AMH was measured in ff and cell-conditioned media (CM).AMH levels in ff and GC-CM ranged from 42 to 2240 and 0.025 to 1.7 ng/ml, respectively, and were low or undetectable in ff and GC-CM from follicles greater than 9 mm, luteinized cells, and theca and stroma. The mean level of AMH was four times higher in GC-CM from ovulatory PCOs [mean (range) 1.56 (0.025-7)] and 75 times higher from anovPCO [21.4 (17.2-43 ng/ml)] than normal ovaries [0.37 (0.025-1.7)]. Neither LH nor FSH had an effect on AMH production by GCs from normal ovaries, but in cells from PCOs, FSH significantly decreased AMH, and in contrast, LH increased AMH.The reduction of AMH in follicles greater than 9 mm from normal ovaries appears to be an important requirement for the selection of the dominant follicle. AMH production per GC was 75 times higher in anovPCOs, compared with normal ovaries. This increase in AMH may contribute to failure of follicle growth and ovulation seen in polycystic ovary syndrome.