Effects of Dexamethasone Administration to Pregnant Rats on Adenylate Cyclase and Cyclic AMP Phosphodiesterase Activities in the Maternal and Fetal Lungs

Abstract

Adenylate cyclase and cyclic AMP phosphodiesterase activities were examined in the maternal and fetal lungs before and after delivery from the saline- and dexamethasone-treated pregnant rats. Basal adenylate cyclase activity in the maternal lungs of control animals did not change after parturition whereas the enzyme activity in fetal lungs increased 2.5-fold after birth. Dexamethasone treatment reduced adenylate cyclase activity in the maternal lungs before and after parturition while the enzyme activity in fetal lungs was increased. The ability of the cytoplasmic factors to activate adenylate cyclase in maternal lungs decreased after parturition. Dexamethasone treatment of the pregnant rat lowered the cytoplasmic activation of the maternal enzyme before and after parturition, but the percent activation of the enzyme in both the maternal and fetal lungs was not affected. The decrease in activator activity of the maternal lungs after parturition was not apparently due to the reduced sensitivity of adenylate cyclase to the same level of the activator protein. However, it would appear that both adenylate cyclase and its activator protein have undergone some maturational changes during lung development. Adrenalectomy of rats did not alter the basal adenylate cyclase activity in lung membranes but reduced the cytoplasmic activation of the enzyme. Unlike pregnant rats, dexamethasone treatment of adrenalectomized rats restored the cytoplasmic activation of adenylate cyclase not only to the control value, but potentiated it even higher than the control without affecting the basal adenylate cyclase activity. Cyclic AMP phosphodiesterase activity in both the maternal and fetal lungs was not influenced by parturition. However, dexamethasone treatment lowered cyclic AMP phosphodiesterase activity in both the maternal and fetal lungs at both ages. Dexamethasone treatment of pregnant rats elevated phospholipids and lowered DNA levels in the maternal as well as fetal lungs. These data are consistent with the view that dexamethasone treatment of pregnant rats during late gestation may elevate cyclic AMP levels to induce fetal lung maturation with a concomitant decrease in cellular proliferation.

Endocrine Control of Cytosolic Factors Stimulating Adenylate Cyclase in Rat Lung

“…The results implicate that glucocorticoids increase the intracellular levels of cyclic AMP by decreasing the PDE activity (Table 3; Sneft et al 1968) as well as by enhancing the adenylate cyclase activity (Table 4). This confirms and extends our previous observation that glucocorticoids probably increase the adenylate cyclase activity (Chaudhary et al 1981;Chaudhary and Nijjar 1984) but the exact mechanism is yet to be established. Endocrine removal and hormone treatment did not effect significantly the phospholipid content of surfactant fraction.…”

Single Dose Versus Two Doses of Betamethasone for Lung Maturation in Preterm Rabbits

“…In the experimental studies and in clinical practice, multiple dosing schedules have been generally used (1, 13). However, single doses of maternal corticosteroids for intervals as short as 24 h were shown to induce surfactant proteins (14,15) and to induce lung choline-phosphate cytidyltransferase and the adenylate cyclase system in fetal rats (16,17). A uniform observation in rodents is that maternal corticosteroids also cause fetal growth retardation (18).…”