SRC TYROSINE KINASE-ACTIVITY IS RELATED TO LUTEINIZING-HORMONE RESPONSIVENESS - GENETIC MANIPULATIONS USING MOUSE MA10 LEYDIG-CELLS

The Src family of tyrosine kinases play an important role in various s ignal transduction pathways in many different cell types, however, the role of these kinases in steroidogenic cells has not been examined. I n the present study, genetic approaches were used to directly alter Sr c tyrosine kinase activity in mouse MA10 Leydig cells in order to dete rmine the effect of changes of Src activity on LH-responsiveness with regard to cAMP and progesterone secretion. MA10 cells expressing a dom inant negative Src (MA10(Srck-3)) secreted more cAMP and progesterone in response to LH than control transfected cells. Phosphodiesterase ac tivity was decreased in MA10(Srck-3) cells. Conversely, MA10 cells exp ressing a temperature sensitive Src (MA10(tsUP)) lost LH-responsivenes s with regard to cAMP and progesterone secretion at the Src active tem perature (35 degrees C). It is concluded that Src tyrosine kinase has an important role in regulating steroid secretion in MA10 Leydig cells . This regulation may in part be due to Src modulation of phosphodiest erase activity, although other components of the LH-signaling pathway may be involved.