Glucocorticoids increase pulmonary beta-adrenergic receptors in fetal rabbit.
beta-Adrenergic agonists stimulate surfactant release and decrease fluid in lung alveoli of fetuses. Both effects are most evident toward the end of gestation. We used [3H] dihydroalprenolol (DHA) to investigate the development of pulmonary beta-adrenergic receptors in rabbit fetuses and to study the effect of glucocorticoid treatment on the beta-receptor number. In the lung particulate preparation, DHA binding was rapid, reversible, stereoselective, and of high affinity. The order of potency for adrenergic agonists in competing for DHA binding was isoproterenol > epinephrine = norepinephrine, which is typical of interactions at a beta 1-adrenergic receptor. Using DHA, we demonstrated that the concentration of pulmonary beta-receptors increased significantly between 28 and 31 days of gestation; however, there was no change in the dissociation constant during gestation. After injecting betamethasone (0.17 mg/kg, 24 hours) into rabbits at 25 days of pregnancy, we found that the concentration of pulmonary beta-receptors increased from 44.2 +/- 6.6 fmol/mg protein in untreated fetuses to 77.9 +/- 5.6 fmol/mg protein in treated fetuses. However, this treatment did not affect the DHA binding sites in the fetal rabbit heart. Maternal treatment with the T3 analogue 3,5-dimethyl-3'-isopropyl-L-thyronine (0.5-1 mg/kg) at a dosage which increased both surfactant synthesis and release did not alter pulmonary receptor concentration. Our results indicate that the concentration of pulmonary beta-adrenergic receptors increases in the fetus at term and suggest that this increase is stimulated by endogenous glucocorticoid in fetal circulation.
D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D004082:Dihydroalprenolol / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D001623:Betamethasone