REGULATION OF FOLLISTATIN MESSENGER-RIBONUCLEIC-ACID IN CULTURED RAT GRANULOSA-CELLS

The regulation of the follistatin mRNA by hormones and endocrine manip ulations was examined in granulosa cell cultures. The follistatin mRNA accumulation was stimulated in a dose-dependent manner by follicle-st imulating hormone (FSH) with a maximal response twice as great as in c ontrol cultures at a dose of 100 ng/ml FSH. The time course of the FSH effect on follistatin mRNA had a biphasic effect in which FSH increas ed follistatin mRNA within 2 h, and subsequently reduced it to below t he control level. 8-Br-8-brom-adenosine 3,5-cyclic monophosphate (cAMP ) (2 mM) and phorbol 12-myristate 13-acetate (PMA) (10 nM) induced a t ime-dependent increase in follistatin mRNA levels, with the maximal re sponse at 6 h and 2 h, respectively. Co-treatment of the granulosa cel ls with cAMP and PMA demonstrated that 0.2 mM of 8-Br-cAMP suppressed the follistatin mRNA of the control and the samples with a small amoun t of PMA in the granulosa cells. Follistatin expression is therefore r egulated by protein kinase A and protein kinase C pathways in rat gran ulosa cells. A more dramatic stimulation of follistatin mRNA was obser ved when this culture was treated with activin, and follistatin also b locked the effect of activin on the follistatin mRNA.