Abstract
Summary: β-Adrenergic receptors were identified in membrane fractions of rat lung with the β-adrenergic antagonists (–)-[3H]-dihydroalprenolol ((–)-[1H]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 β-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; by day 28 somatic and lung weight, lung DNA, and protein were markedly decreased in hypothyroid pups as compared to controls. Pulmonary β-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 β-adrenergic receptors to near normal concentrations by day 28. We conclude that thyroid hormones or thyroid dependent factors enhance pulmonary β-adrenergic receptor synthesis and that thyroid hormone is required for the normal postnatal maturation of the β-adrenergic receptor system in the rat lung.
Speculation: Thyroid hormone or thyroid hormone dependent factors are required for the normal postnatal growth and maturation of the rat lung. Pulmonary β-adrenergic receptors increase markedly during the wrinatal wriod in the rat and their normal postnatal developmeit is thyroid hormone dependent. Because the timing of increased thyroid gland activity varies among species, occurring earlier in the human than in the rat, the possible effects of thyroid hormone on pulmonary maturation in the human might also occur at an earlier time in perinatal life. Finally, it is speculated that the ontogenic increases in pulmonary β-adrenergic receptors are also associated with developmental changes in catecholamine mediated cellular responses of specific pulmonary cells.
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Whitsett, J., Darovec-Beckerman, C., Pollinger, J. et al. Ontogeny of β-Adrenergic Receptors in the Rat Lung: Effects of Hypothyroidism. Pediatr Res 16, 381–387 (1982). https://doi.org/10.1203/00006450-198205000-00013
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DOI: https://doi.org/10.1203/00006450-198205000-00013