Regulation of isoproterenol-stimulated DNA synthesis in rat salivary gland in vivo by adrenal glucocorticoids

Abstract

The magnitude of isoproterenol-stimulated DNA synthesis in rat liver submandibular gland varies 20-fold, depending on the time of day of drug injection, although diurnal regulation is not altered by aging. The diurnal response to isoproterenol reflects largely the hour to hour nutritional status of the rats as indicated by the inability of the drug to stimulate DNA synthesis in rats deprived of food for as little as 18 hr. Administration of glucocorticoids whose serum levels increase during fasting, in dosages as low as 0·05 mg per 100 g of body weight, both delays and reduces the magnitude of isoproterenol-stimulated DNA synthesis in rat submandibular gland. Inhibitory action of cortisol is effective when administered up to 8 hr following isoproterenol injection, and may be related to the delay in an Actinomycin D-sensitive event, required for DNA synthesis, which normally is stimulated at about that time. That isoproterenol-stimulated DNA synthesis may be regulated in vivo by endogenous glucocorticoids is indicated by: (1) acceleration and increased magnitude of isoproterenol-stimulated DNA synthesis in adrenalectomized rats; (2) inhibitory effects of corticosterone, the predominant glucocorticoid in rat, similar to those of cortisol; (3) specific binding of [ 3H]-corticol, [ 3H]-corticosterone and [ 3H]-dexamethasone to macromolecules derived from cytoplasmic extracts of submandibular gland; and (4) reduced uptake of [ 3H]-steroid following injection of isoproterenol.