Regulation of tyrosine hydroxylase by cyclic AMP and dexamethasone in mouse neuroblastoma cells

Abstract

Cyclic AMP has been shown to mediate the induction of TH in the adrenal medulla and in adrenergic mouse neuroblastoma cell lines (Waymire et al., 1972; Guidotti and Costa, 1973; Richelson, 1973). In the adrenal medulla Costa and coworkers (Costa et al., 1977) have shown that an increase in cyclic AMP which persists for 1–2 hours is associated with activation of cyclic AMP-dependent protein kinase, translocation of the catalytic subunit of protein kinase from the cytosol to the nucleus, and the subsequent induction of TH. Glucocorticoids have been shown to induce TH in the rat superior cervical ganglion (SCG) and in rat pheochromocytoma cells (Otten and Thoenen, 1976; Lucas and Thoenen, 1977; Schubert et al., 1980). Using organ cultures of the rat SCG and the glucocorticoid analog, dexamethasone, Otten and Thoenen (1976) have demonstrated that the dexamethasone-mediated induction of TH requires presynaptic innervation, that a four-hour exposure to dexamethasone yields maximal induction and that the effect is dose-dependent and maximal at 10⁻⁷ M dexamethasone.