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Reduced Gonadotropin Responses in a Novel Clonal Strain of Leydig Tumor Cells Established by Transfection of MA-10 Cells with a Mutant Gene of the Type I Regulatory Subunit of the cAMPDependent Protein Kinase

The Population Council New York, New York 10021

Address requests for reprints to: Dr. Mario Ascoli, The Population Council, 1230 York Avenue, New York, New York 10021.

Abstract

Although it is clear that cAMP is an important mediator of the actions of LH/CG in Leydig cells, recent studies from several laboratories have shown that the functions of Leydig cells can also be modulated by hormones and growth factors that do not appear to use cAMP as a second messenger. Thus, in order to increase our understanding of the importance of cAMP as a modulator of the functions of Leydig cells we have used a genetic approach to establish permanent cell lines that express a cAMP-resistant phenotype.

MA-10 cells, a clonal strain of cultured Leydig tumor cells that express many of the characteristics of normal Leydig cells, were transfected with an expression vector controlled by the metallothionein promoter and encoding for a mutant form of the regulatory subunit of the type I cAMP-dependent protein kinase. Three stable transfectants that display a Zn⁺²-dependent decrease in cAMP-dependent protein kinase activity were established. Further characterization of one of the transfectants (designated MA-10(K3)) revealed a parallel reduction in the ability of cAMP and human CG to induce cell rounding, to increase steroid synthesis, or to induce c-fos mRNA.

Our initial studies on these mutant cells have already provided novel information about the actions of human CG. These cell lines will also be valuable for further studies on the signaling systems that mediate hormone action in Leydig cells.

FOOTNOTES

This work was supported by NIH Grant CA-40629. Cyclic AMP Resistant Mutants of MA-10 Cells

^* Supported by a fellowship from the Andrew W. Mellon Foundation.

Received for publication September 21, 1989. Revision received October 17, 1989. Accepted for publication October 17, 1989.

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