Retinoic Acid (RA) Represses Follicle Stimulating Hormone (FSH)-Induced Luteinizing Hormone (LH) Receptor in Rat Granulosa Cells

The present study was undertaken to identify the mechanisms underlying the effect of retinoic acid (RA) on the luteinizing hormone receptor (LH-R) in rat granulosa cells. Treatment with FSH produced a substantial increase in LH-R mRNA level, as was expected, while concurrent treatment with increasing concentrations of RA brought about dose-dependent decreases in FSH-induced LH-R mRNA. RA, either alone or in combination with FSH, did not affect intracellular cAMP levels, while it inhibited the effect of 8-Br-cAMP on LH-R mRNA production. Whether the effect of RA and FSH on LH-R mRNA levels was the result of decreased transcription and/or altered mRNA stability was also investigated. The rate of LH receptor mRNA gene transcription, assessed by nuclear run-on transcription assay, was inhibited by the addition of RA. The effect of RA on LH-R mRNA stability was determined by measuring the decay of LH receptor mRNA under conditions known to inhibit transcription. The decay curves for the 5.4-kb LH-R mRNA transcript showed a significant decrease after the addition of RA. It may be possible that RA not only inhibits FSH-induced transcription but also stimulates the production of destabilizing factors for the LH-R mRNA. These findings assist in understanding the molecular mechanism underlying the effect of RA on reproductive function in rat granulosa cells.