INDUCTION OF AROMATASE IN HUMAN GRANULOSA-CELLS BY BOTH FOLLICLE-STIMULATING-HORMONE AND INSULIN-LIKE GROWTH-FACTOR-I INVOLVES TYROSINE PHOSPHORYLATION

Evaluation of the intracellular signalling mechanisms of follicle stim ulating hormone (FSH) and insulin-like growth factor-I (IGF-I) was per formed in luteinized and non-luteinized human granulosa cells. A sever alfold increase in estradiol production from androstenedione was induc ed by both hormones in these cells, while only FSH led to a concomitan t increase in cAMP. IGF-I bound specifically to its receptor in these cells. Specific tyrosine kinase inhibitors (tyrphostins) blocked the e ffects of both FSH and IGF-I on aromatase activity without altering FS H-induced cAMP accumulation. These findings demonstrate an involvement of a tyrosine kinase pathway in the intracellular signalling mechanis m of the IGF-I effect on aromatase activity. Furthermore, since FSH in duction of aromatase activity can be blocked by a tyrosine kinase inhi bitor without affecting the level of cAMP production, it can be sugges ted that tyrosine kinase(s) act downstream of cAMP production and prot ein kinase A activation.