A CYTOSOLIC PROTEIN-TYROSINE KINASE-ACTIVITY IS INDUCED BY FOLLICLE-STIMULATING-HORMONE AND INSULIN-LIKE GROWTH-FACTOR-I IN HUMAN GRANULOSA-CELLS

Follicle stimulating hormone (FSH) induces estradiol (E(2)) production in rat, porcine and human granulosa cells with a concomitant increase in cAMP. In human granulosa cells insulin like growth factor-I (IGF-I) induces E(2) production without cAMP accumulation. In the current study we report that IGF-I and FSH effects on aromatase activity both involve activation of a cytosolic soluble protein tyrosine kinase (CytPTK). This FSH and IGF-I stimulated CytPTK activity was blocked by AG-82 (a tyrosine kinase inhibitor) and by staurosporine (STS) (a non specific protein kinase inhibitor) at concentrations which inhibited E(2) production. These new findings strengthen the concept of fail-safe mechanism in E(2) production in human granulosa cells by an involvement of tyrosine kinase(s) activity downstream of cAMP formation and protein kinase A (PKA) activation.