The mRNA encoding a high-affinity cAMP phosphodiesterase is regulated by hormones and cAMP.
To elucidate the mechanisms by which hormones regulate cAMP phosphodiesterases (PDEs), a group of cDNA clones that had been isolated from a rat Sertoli cell library were characterized. These cDNAs are derived from a single gene (ratPDE3). The deduced amino acid sequence of the ratPDE3 cDNA corresponds to a 66,200-Da protein homologous to other testicular PDEs, to the Drosophila melanogaster dunce-encoded cAMP PDE, and to bovine and yeast PDEs. Expression of ratPDE3 in eukaryotic and prokaryotic cells leads to the appearance of a cAMP PDE with properties identical to the cAMP PDE purified from Sertoli cells. Although of different size, transcripts corresponding to ratPDE3 were present in all organs studied. In the immature Sertoli cell in culture, the level of mRNA transcripts of ratPDE3 was increased more than 100-fold by follicle-stimulating hormone or N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate treatment. Stimulation of ratPDE3 mRNA by N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate was also observed in a C6 glioma cell line. These data demonstrate that cAMP regulates the expression of one of its own degrading enzymes by an intracellular feedback mechanism that involves changes in mRNA levels.
Swinnen
J V
JV
Department of Pediatrics, University of North Carolina, Chapel Hill 27599.
Joseph
D R
DR
Conti
M
M
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015723:Gene Library; D005796:Genes / Q000187:drug effects; D005910:Glioma; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012708:Sertoli Cells / Q000201:enzymology*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D012333:RNA, Messenger; D003994:Bucladesine; D005640:Follicle Stimulating Hormone; D004247:DNA; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases