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.