Hormonal Regulation of Cyclic Nucleotide Phosphodiesterases*

ACOMPLEX array of signals from the extracellular environment regulate many cell processes, including the entry and exit from the mitotic cycle and the induction and maintenance of differentiation (1–3). Cells elaborate these external stimuli via receptors, transducers, and second messengers (4, 5) which control intricate circuits that lead to protein phosphorylation by protein kinases (6, 7). Although novel second messenger pathways have been discovered and dissected in some detail in the past 10 years (8, 9), cyclic nucleotides (cAMP and cGMP) remain the best characterized second messengers, and their role in the differentiation and control of metabolic processes of the endocrine cell is widely recognized. The components of the membrane-associated machinery that transduces external signals into changes in cyclic nucleotide levels have been isolated and characterized. These include many members of the family of membrane receptors (10–14), G proteins acting as transducers (15, 16), and adenylate cyclase effectors (15, 17). Furthermore, complementary DNAs that encode these components are becoming available (10–17), thus opening new avenues by which to study the structure and function of these membrane-associated, protein complexes.