Control of the Expression of Luteinizing Hormone Receptor by Local Factors in Rat Granulosa Cells

To identify the mechanisms underlying the hormone-dependent induction and maintenance of luteinizing hormone receptor (LH-R) in rat granulosa cells, the effect of follicle-stimulating hormone (FSH) and local factors on the LH-R mRNA levels were studied. LH-R mRNA levels of the cells incubated with FSH decreased rapidly after medium removal, and readdition of FSH with the fresh medium did not restore these levels. On the other hand, 8-bromoadenosine 3,5-cyclic monophosphate significantly enhanced the expression of LH-R mRNA after medium removal, while the level of LH-R mRNA was lower than that of the cells replaced by original medium including FSH. In addition, the incubation with 8-Br-cAMP produced dose-dependent responses for LH-R mRNAs and enhanced the activity of 1379 bp of the LH-R 5′-flanking region, while the level of LH-R mRNA decreased 3 days after medium removal. Further studies were undertaken to assess the role of factors in maintaining the LH receptor once induced by FSH. Since FSH and cAMP increase follistatin production in granulosa cells, we examined the effect of follistatin on LH-R induction in the presence of activin and FSH. Activin induced LH-R in the presence of FSH significantly, and follistatin antagonized this effect in a dose-dependent manner. However, insulinlike growth factor-I (IGF-I) induced LH-R mRNA in the presence of FSH even after medium change. IGF-I might be one of the important factors that act in the medium to maintain LH-R levels in granulosa cells.