DISTINCTIVE ANATOMICAL PATTERNS OF GENE-EXPRESSION FOR CGMP-INHIBITEDCYCLIC-NUCLEOTIDE PHOSPHODIESTERASES

Type III cGMP-inhibited phosphodiesterases (PDE3s) play important role s in hormonal regulation of lipolysis, platelet aggregation, myocardia l contractility, and smooth muscle relaxation. We have recently charac terized two PDE3 subtypes (PDE3A and PDE3B) as products of distinct bu t related genes. To elucidate their biological roles, in this study we compare cellular patterns of gene expression for these two enzymes du ring rat embryonic and postnatal development using in situ hybridizati on. PDE3A mRNA is abundant in adipose tissue and is also expressed in hepatocytes throughout development. This mRNA is also highly abundant in embryonic neuroepithelium including the neural retina, but expressi on is greatly reduced in the mature nervous system. Finally, PDE3A mRN A is localized in spermatocytes and renal collecting duct epithelium i n adult rats. PDE3B mRNA is highly expressed in the cardiovascular sys tem, including myocardium and arterial and venous smooth muscle, throu ghout development. It is also abundant in bronchial, genitourinary and gastrointestinal smooth muscle and epithelium, megakaryocytes, and oo cytes. PDE3B mRNA demonstrates a complex, developmentally regulated pa ttern of gene expression in the central nervous system. In summary, th e two different PDE3s show distinctive tissue-specific patterns of gen e expression suggesting that PDE3A is involved in hormonal regulation of lipolysis and glycogenolysis, while regulation of myocardial and sm ooth muscle contractility appears to be a function of PDE3B. In additi on, the present findings suggest previously unsuspected roles for thes e enzymes in gametogenesis and neural development.