EFFECT OF ACTIVIN ON LUTEINIZING HORMONE-HUMAN CHORIONIC-GONADOTROPIN RECEPTOR MESSENGER-RIBONUCLEIC-ACID IN GRANULOSA-CELLS

Activin (the dimer of inhibin beta-subunit) is involved in the modulation of granulosa cell function. Recent reports have indicated that activin had an effect on LH/human CG (hCG) receptor induction and steroidogenesis in granulosa cells. To characterize the regulation inducing LH/hCG receptor by activin, we investigated messenger RNA (mRNA) levels, the expression of the LH/hCG receptor, and intracellular cAMP accumulation in cultured rat granulosa cells. Northern blot analysis showed an increase in the LH/hCG receptor mRNA level with FSH (30 ng/ml) and activin (100 ng/ml) cotreatment, whereas activin alone could not augment LH/hCG receptor mRNA at all. After the addition of actinomycin D to the culture medium, LH/hCG receptor mRNA was more stable in the presence of FSH plus activin than in the presence of FSH alone. Similarly, a receptor binding assay revealed that the cotreatment with FSH and activin induced more LH/hCG receptor than FSH alone 96 h after exposure to hormone, but that activin (100 ng/ml) alone could not induce the LH/hCG receptor. Since the primary, if not the sole, second messenger mediating the action of FSH in granulosa cells has been shown to be cAMP, intracellular cAMP accumulation was measured in granulosa cells in the presence of FSH (30 ng/ml) and/or activin (100 ng/ml). Although FSH-stimulated cAMP accumulation reached a peak 15 min after incubation, activin did not significantly alter cAMP accumulation in either control nor FSH-stimulated granulosa cells, indicating that the effects of activin on the LH/hCG receptor in granulosa cells are not mediated by the increase in cAMP. These results demonstrate that activin enhances the FSH-induced LH/hCG receptor mRNA, LH/hCG receptor mRNA stability, and LH/hCG binding sites not due to the stimulation of the adenylate cyclase system. Although the signal pathway from the activin receptor has not been elucidated upon yet, activin is capable of increasing LH/hCG receptor levels through the accumulation of LH/hCG receptor mRNA levels.