Induction of aromatase in human granulosa cells by both follicle stimulating hormone and insulin-like growth factor-I involves tyrosine phosphorylation

Gynecol Endocrinol. 1994 Sep;8(3):183-9. doi: 10.3109/09513599409072453.

Abstract

Evaluation of the intracellular signalling mechanisms of follicle stimulating hormone (FSH) and insulin-like growth factor-I (IGF-I) was performed in luteinized and non-luteinized human granulosa cells. A severalfold increase in estradiol production from androstenedione was induced by both hormones in these cells, while only FSH led to a concomitant increase in cAMP. IGF-I bound specifically to its receptor in these cells. Specific tyrosine kinase inhibitors (tyrphostins) blocked the effects of both FSH and IGF-I on aromatase activity without altering FSH-induced cAMP accumulation. These findings demonstrate an involvement of a tyrosine kinase pathway in the intracellular signalling mechanism of the IGF-I effect on aromatase activity. Furthermore, since FSH induction of aromatase activity can be blocked by a tyrosine kinase inhibitor without affecting the level of cAMP production, it can be suggested that tyrosine kinase(s) act downstream of cAMP production and protein kinase A activation.

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Adult
  • Aromatase / biosynthesis*
  • Catechols / pharmacology
  • Cells, Cultured
  • Cyclic AMP / analysis
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cyclic AMP-Dependent Protein Kinases / physiology
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Enzyme Induction
  • Estradiol / biosynthesis
  • Female
  • Follicle Stimulating Hormone / pharmacology*
  • Granulosa Cells / cytology
  • Granulosa Cells / drug effects
  • Granulosa Cells / enzymology*
  • Granulosa Cells / metabolism
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology*
  • Middle Aged
  • Nitriles / pharmacology
  • Phosphorylation / drug effects
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Tyrosine / metabolism*
  • Tyrphostins*

Substances

  • Catechols
  • Nitriles
  • Tyrphostins
  • tyrphostin 47
  • Tyrosine
  • Estradiol
  • Insulin-Like Growth Factor I
  • Follicle Stimulating Hormone
  • Cyclic AMP
  • Aromatase
  • Protein-Tyrosine Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • Adenylyl Cyclases