Biphasic response to 3',5'-cyclic adenosine monophosphate (cAMP) at the messenger ribonucleic acid level for a regulatory subunit of cAMP-dependent protein kinase

In the present study we have examined the effect of long-term stimulation with (Bu)2cAMP on mRNA levels for the hormone responsive regulatory subunit (RII beta) of cAMP-dependent protein kinase in cultured rat Sertoli cells. The effects of the same treatment on two other mRNAs [androgen binding protein (ABP) and cellular retinol binding protein (cRBP)], shown to be regulated by cAMP, were examined simultaneously. The addition of (Bu)2cAMP (0.1 mM) to primary Sertoli cell cultures, for 14 and 24 h, caused a 50- to 60-fold stimulation in the steady state levels of mRNA for RII beta. During the same period of stimulation, we also observed a significant increase (2- to 3-fold) in the mRNA levels for ABP, and a 80% decrease in the mRNA levels for cRBP. Continued stimulation for 36 and 48 h was associated with a significant time-dependent decrease in the mRNA level for RII beta, in spite of the continuous presence of (Bu)2cAMP (0.1 mM) in the medium. This reduced response by long term stimulation with (Bu)2cAMP appears to be specific for RII beta, since mRNA for ABP remained elevated and mRNA for cRBP remained depressed during the entire period of cAMP stimulation. Our data demonstrate the presence of a biphasic type of regulation at the mRNA level, specific for the regulatory subunit RII beta of cAMP-dependent protein kinase. This response may be analogous to the desensitization mechanisms observed at other levels of the cAMP signalling pathway. For proteins constituting part of the signal transduction pathway this type of biphasic regulation, may be particularly important in maintaining homeostasis in the cell.