The Roles of camp and camp-Dependent Protein Kinase in Forskolin's Actions on Y1 Adrenocortical Tumor Cells

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Abstract
The effects of forskolin on the regulation of steroido-genesis and growth were examined in the Y1 adrenocortical tumor cell line, and the roles of cAMP and cAMP-dependent protein kinase in these actions of forskolin were evaluated. Forskolin, like corticotropin, stimulated steroidogenesis 3-fold and inhibited growth by 90%. In mutants of the Y1 cell line harboring specific defects in cAMP-dependent protein kinase activity, the responses to forskolin were attenuated. The resistance of the protein kinase mutants to the diterpene was closely correlated with their resistance to corticotropin and with impaired responses of their protein kinases to cAMP. These results indicate that cAMP and cAMP-dependent protein kinase are obligatory components of forskolin's actions on Y1 adrenal cells. Forskolin, at concentrations which were approximately 100-times greater than those required to stimulate steroidogenesis, caused cAMP to accumulate. Apparently, only a small fraction of the cAMP generated in response to forskolin was required to stimulate steroidogenesis or inhibit growth.