Ontogeny of beta-adrenergic receptors in the rat lung: effects of hypothyroidism.
Beta-Adrenergic receptors were identified in membrane fractions of rat lung with the beta-adrenergic antagonists (-)-[3H]-dihydroalprenolol (-)-[3H]DHA) and (+/-)-[125I]-iodohydroxybenzylpindolol ((+/-)-[125I]HYP). Binding capacity (Bmax) for (-)-[3H]DHA increased progressively from 46 +/- 7 on day 18 of gestation to 510 +/- 70 femtomoles . mg-1 protein (mean +/- S.D.) on postnatal day 28, at which time adult Bmax was attained. An increase in (-)-[3H]DHA binding capacity of the lung was observed between postnatal days 15 and 28, during the known period of increased thyroid gland secretory activity, serum triiodothyronine (T3), and thyroxine (T4) concentrations in the rat. We therefore studied lung beta-adrenergic receptors in rat pups made hypothyroid with propylthiouracil (PTU) (in utero and postnatally) compared to normal age-matched control pups and to euthyroid pups which were treated with PTU but were also injected daily with thyroxine (T4-treated). Hypothyroid pups grew nearly normally until postnatal day 15 but grew poorly thereafter; but day 28 somatic and lung weight, lung DNA, and protein were markedly decreased in hypothyroid pups as compared to controls. Pulmonary beta-adrenergic receptors were similar in hypothyroid pups and controls on day 15, but were markedly decreased in hypothyroid pups on day 28 (294 +/- 57 versus 489 +/- 82 femtomoles . mg-1 protein in T4 treated euthyroid controls). Treatment of the hypothyroid pups with T4 on day 25 significantly increased lung beta-adrenergic receptors to near normal concentrations by day 28. We conclude that thyroid hormones or thyroid dependent factors enhance pulmonary beta-adrenergic receptor synthesis and that thyroid hormone is required for the normal postnatal maturation of the beta-adrenergic receptor system in the rat lung.
D000818:Animals; D005260:Female; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism*; D008168:Lung / Q000032:analysis* / Q000254:growth & development; D011247:Pregnancy; D011441:Propylthiouracil; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000032:analysis*; D011943:Receptors, Adrenergic, beta / Q000032:analysis*; D013974:Thyroxine / Q000502:physiology
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D011441:Propylthiouracil; D013974:Thyroxine