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 signal transduction pathways in many different cell types, however, the role of these kinases in steroidogenic cells has not been examined. In the present study, genetic approaches were used to directly alter Src tyrosine kinase activity in mouse MA10 Leydig cells in order to determine the effect of changes of Src activity on LH-responsiveness with regard to cAMP and progesterone secretion. MA10 cells expressing a dominant negative Src (MA10(Srck-3)) secreted more cAMP and progesterone in response to LH than control transfected cells. Phosphodiesterase activity was decreased in MA10(Srck-3) cells. Conversely, MA10 cells expressing a temperature sensitive Src (MA10(tsUP)) lost LH-responsiveness with regard to cAMP and progesterone secretion at the Src active temperature (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 phosphodiesterase activity, although other components of the LH-signaling pathway may be involved.