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 increasin g concentrations of RA brought about dose-dependent decreases in FSH-induce d LH-R mRNA. RA, either alone or in combination with FSH, did not affect in tracellular 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 als o investigated. The rate of LH receptor mRNA gene transcription, assessed b y nuclear run-on transcription assay, was inhibited by the addition of Rk T he effect of RA on LH-R mRNA stability was determined by measuring the deca y 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 decre ase after the addition of Rk It may be possible that RA not only inhibits F SH-induced transcription but also stimulates the production of destabilizin g factors for the LH-R mRNA, These findings assist in understanding the mol ecular mechanism underlying the effect of RA on reproductive function in ra t granulosa cells. (C) 2000 Academic Press.