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 (E2) 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 E2 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 E2 production. These new findings strengthen the concept of fail-safe mechanism in E2 production in human granulosa cells by an involvement of tyrosine kinase(s) activity downstream of cAMP formation and protein kinase A (PKA) activation.
Costrici
N
N
Department of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Elberg
G
G
Lunenfeld
B
B
Pariente
C
C
Dor
J
J
Kanety
H
H
Karasik
A
A
D000470:Alkaloids / Q000494:pharmacology; D001141:Aromatase / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015398:Signal Transduction; D019311:Staurosporine
D000470:Alkaloids; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D005640:Follicle Stimulating Hormone; D001141:Aromatase; D011505:Protein-Tyrosine Kinases; D019311:Staurosporine