cAMP-synthesis in a medullary thyroid carcinoma cell line: Response to adrenergic agents and prostaglandines

Calcitonin secretion by C-cells is mediated through intracellular 3'5'-cycl ic adenosine monophosphate (cAMP) and calcium signaling. Calcitonin release stimulation tests may take advantage of both signaling cascades in screeni ng for medullary thyroid carcinomas (MTC). To elucidate the regulation of t he adenylyl cyclase system we have determined cAMP levels of a calcitonin-e xpressing MTC cell line (RC) after exposure to adrenergic agents and prosta glandines. In early passages (20-30) cAMP concentrations were significantly elevated in RG cells after exposure to beta-adrenergic agents and prostagl andines E-1 and E-2. In advanced passages (60-80) the beta-adrenergic respo nse was no longer detectable and adrenergic receptors were uncoupled from t he adenylyl cyclase complex; while the effect of prostaglandines E-1 and E- 2 remained unaffected. Preincubation with dexamethasone, in a process requi ring protein new synthesis, re-established the adrenergic response in later passages, indicating that RC cells dedifferentiated in culture over time. Our in vitro findings suggest that MTC cell dedifferentiation may be accomp anied by adrenergic receptor-uncoupling from the adenylate cyclase system a nd that this process may be reversed by dexamethasone incubation.