The mechanisms of retinoic acid-induced regulation on the follicle-stimulating hormone receptor in rat granulosa cells

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 increase in FSH-R mRNA level, as was expected, while concurrent treatment with increasing concentrations of RA brought about dose-dependent decreases in FSH-induced FSH-R mRNA, with a maximal inhibition one-third lower than that induced by FSH alone. RA, either alone or in combination with FSH, did not affect intracellular cAMP levels, while it inhibited the effect of 8-Br-cAMP on FSH-R mRNA production. These results suggested that RA diminished the action of FSH on FSH-R expression at sites distal to cAMP generation in the granulosa cells. Whether the effect of RA and FSH on FSH-R mRNA levels was the result of decreased transcription and/or altered mRNA stability was also investigated. The rate of FSH receptor mRNA gene transcription, assessed by 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 transcript 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 that the effect of RA on FSH-R expression is possibly mediated by the reduction 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 granulosa cells. (C) 2000 Published by Elsevier Science B.V. All rights reserved.