INTERACTION BETWEEN ACTIVIN-A AND CAMP IN THE INDUCTION OF FSH RECEPTOR IN CULTURED RAT GRANULOSA-CELLS

The acquisition of FSH receptor during preantral folliculogenesis is b elieved to be a key step in the subsequent development of follicles. W e examined the interaction between activin and cAMP in FSH receptor in duction in rat granulosa cells by measuring I-125-FSH binding and FSH receptor mRNA. In the I-125-FSH binding study, 0.2 mM 8-Br-cAMP and 1 mu M forskolin were maximally effective in FSH receptor induction (169 and 220% respectively of control), while higher concentrations gave a ttenuated responses. It appears that cAMP has ambivalent effects on FS H receptor induction depending on the concentration and length of expo sure. Activin alone dramatically increased the number of FSH receptors (314% of control). Moreover, synergistic effects of activin and 8-Br- cAMP or forskolin were observed on FSH receptor induction: a combinati on of activin (80 ng/ml) and low doses of 8-Br-cAMP (0.2 mM) or forsko lin (1 mu M) was most effective (160 or 140% of that induced by activi n alone) and receptor levels reached a maximum at 24 h. These levels t hen markedly decreased after 72 h of incubation. Northern blot analysi s revealed that the combination of activin (80 ng/ml) and 8-Br-cAMP (0 .2 mM) or forskolin (1 mu M) increased FSH receptor mRNA to about 140% of that induced by activin alone. These results indicate that activin and cAMP induced FSH receptor synergistically. However, activin did n ot enhance the production of cAMP induced by forskolin. In addition, a protein kinase A inhibitor (H89) (2 mu M), which inhibited the effect s of forskolin, had no effect on the action of activin. Taken together , the present findings suggest that the action of activin is not via a cAMP pathway, and that activin works co-operatively with cAMP on foll iculogenesis.