The aim of this study was to explore the direct action of
acetylcholine on
gonadotropin-stimulated progesterone (P) and estradiol (E(2))
secretion of human
granulosa cells (GCs) cultured in serum-free medium. Human GCs
were isolated from
preovulatory follicular fluid aspirated from 22 women undergoing
in vitro
fertilization at the University Women's Hospital of Tubingen.
The production of
progesterone and E(2) was measured in the presence and absence
of acetylcholine,
carbachol, atropine, luteinizing hormone (LH) or follicle-
stimulating hormone
(FSH) using radioimmunoassay. Statistical analysis of the data
was performed by
ANOVA and Newman-Keuls test. Administration of acetylcholine or
carbachol (10(-5)
M) resulted in a significant increase in P and E(2) secretion.
This response was
specifically blocked by the muscarinic receptor antagonist
atropine. Similarly,
carbachol resulted in a significant increase in P and E(2)
output, though the
response to it was somewhat reduced when compared to that evoked
by
acetylcholine. Acetylcholine did not show any additive effect on
LH-stimulated P
secretion, while it augmented the stimulatory effect of FSH on P
release. In
contrast, carbachol markedly diminished the stimulatory effect
of LH on P
secretion, while it caused no change in FSH-induced P output.
When administered
together, acetylcholine did not modify the stimulatory effect of
FSH on E(2)
secretion, however, it markedly elevated LH-induced E(2) output.
Similar to this,
carbachol significantly increased LH-induced E(2) release,
however it decreased
FSH-stimulated E(2) secretion. We suggest that acetylcholine has
a direct
modulatory effect on gonadotropin-stimulated steroid production
of GCs, an effect
that is mediated via muscarinic receptors. This effect may have
a physiological
role in the regulation of GC function during the menstrual
cycle.
