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Adenosine 3',5'-Monophosphate-Dependent Stabilization of Messenger Ribonucleic Acids (mRNAs) for Protein Kinase-A (PKA) Subunits in Rat Sertoli Cells: Rapid Degradation of mRNAs for PKA Subunits Is Dependent on Ongoing RNA and Protein Synthesis^*

Institute of Medical Biochemistry, University of Oslo Oslo, Norway

Address all correspondence and requests for reprints to: Helle K. Knutsen, Institute of Medical Biochemistry, University of Oslo, POB. 1112 Blindern, 0317 Oslo 3, Norway.

Abstract

cAMP treatment of primary cultures of Sertoli cells is associated with a transient stimulatory effect on mRNA levels for various protein kinase-A (PKA) subunits. We have previously shown that the induction of mRNA for regulatory subunit II/3 (RIIβ) is due at least partly to transcriptional activation. In the present study we investigate possible regulatory effects of (Bu)2cAMP on the degradation of mRNAs for various PKA subunits in rat Sertoli cells.

We demonstrate subunit specific differences in the decay of mRNAs for the various PKA subunits. When (Bu)₂cAMP was removed from Sertoli cell cultures after 6 h of stimulation, there was a rapid decay of mRNAs for both RIIβ and RIa (half-lives, -3 h). In contrast, mRNA levels for Rlla continued to increase. Removal of (Bu)²cAMP after a longer period of treatment revealed a similar decay of mRNAs for all of the PKA subunits, with half-lives of approximately 3 h.

Incubation of Sertoli cells for 12 h with (Bu)₂cAMP, followed by continued incubation in the absence and presence of (Bu)₂cAMP as well as in the presence of actinomycin-D (an inhibitor of RNA synthesis), revealed (Bu)₂cAMP mediated stabilization of mRNA for the RIIβ subunit.

Interestingly, actinomycin-D as such stabilized mRNAs for all PKA subunits. Similar treatment with cycloheximide (an inhibitor of protein synthesis) revealed distinct differences between the RI and C subunits vs. the RII subunits; cycloheximide reduced the decay of both RIIjS and Rlla mRNAs, whereas steady state levels of mRNAs for RIa and Ca actually increased after cycloheximide treatment of previously (Bu)₂cAMP-stimulated cultures. Cycloheximide treatment also increased basal levels of mRNAs for RIa and Ca, whereas basal levels of RIIβ and Rlla mRNAs were not influenced.

These studies indicate that the degradation of mRNAs for the various PKA subunits is subject to different regulation by (Bu)₂cAMP, and that ongoing RNA and protein synthesis is required for rapid degradation of all PKA subunits. (Endocrinology 129: 2496–2502, 1991)

Footnotes

^* This work was supported by the Norwegian Cancer Society, the Norwegian Research Council for Science and Humanities, the Nordic Insulin Foundation, the Astri and Birger Torsteds Foundation, and the Anders Jahre Foundation.

Received April 9, 1991.

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