T. Minegishi et al., The mechanisms of retinoic acid-induced regulation on the follicle-stimulating hormone receptor in rat granulosa cells, BBA-MOL CEL, 1495(3), 2000, pp. 203-211
Citations number
47
Categorie Soggetti
Cell & Developmental Biology
Journal title
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
The present study was undertaken to identify the mechanisms underlying the
effect of retinoic acid (RA) on follicle-stimulating hormone receptor (FSH-
R) in rat granulosa cells. Treatment with FSH produced a substantial increa
se in FSH-R mRNA level, as was expected, while concurrent treatment with in
creasing concentrations of RA brought about dose-dependent decreases in FSH
-induced FSH-R mRNA, with a maximal inhibition one-third lower than that in
duced by FSH alone. RA, either alone or in combination with FSH, did not af
fect intracellular cAMP levels, while it inhibited the effect of 8-Br-cAMP
on FSH-R mRNA production. These results suggested that RA diminished the ac
tion of FSH on FSH-R expression at sites distal to cAMP generation in the g
ranulosa cells. Whether the effect of RA and FSH on FSH-R mRNA levels was t
he result of decreased transcription and/or altered mRNA stability was also
investigated. The rate of FSH receptor mRNA gene transcription, assessed b
y nuclear run-on transcription assay, was found to decrease by the addition
of RA. On the other hand, the decay curves for the 2.4 kb FSH-R mRNA trans
cript in primary granulosa cells did not alter the slope of the FSH-R mRNA
decay curve in the presence of RA. Our data suggests for the first time tha
t the effect of RA on FSH-R expression is possibly mediated by the reductio
n of the FSH-R mRNA level due to a negative regulation of the FSH-R gene in
the presence of FSH. These findings assist in understanding the molecular
mechanism underlying the effect of RA on reproductive function in rat granu
losa cells. (C) 2000 Published by Elsevier Science B.V. All rights reserved
.