((f)-[12611HYP). Binding capacity (B, , ) for (-)-I3H]DHA increased progressively from 46 + 7 on day 18 of gestation to 510 2 70 femt~moles*mg-~ protein (mean + S.D.) on postnatal day 28, at which time adult B, , was attained. An increase in (-)-i3HI 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 /?-adrenergic receptors in rat pups made hypothyroid with propylthiouracil (PTU) (in utero and postnatally) compared to normal agematched control pups and to euthyroid pups which were treated with PTU but were also injected daily with thyroxine (T4treated). 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 Padrenergic receptors were similar in hypothyroid pups and controls on day 15, but were markedly decreased in hypothyroid pups on day 28 (294 2 57 versus 489 + 82 femtomoles*mg-' protein in T4 treated euthyroid controls). Treatment of the hypothyroid pups with T4 on day 25 significantly increased lung ~a d r e n e r~i c receptors to near normal concentrations bv dav 28. We conclude that thvroid hormones or thyroid dependent faftors enhance pulmonary b-adrenergic recep tor synthesis and that thyroid hormone is required for the normal postnatal maturation of the 8-adrenergic receptor system in the rat lung. SpeculationThyroid hormone or thyroid hormone dependent factors are required for the normal postnatal growth and maturation of the rat lung. Pulmonary &adrenergic-receptors increase markedly during the wrinatal wriod in the rat and their normal postnatal developmeit is thyroib hormone dependent. Because themtiming 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 /?-adrenergic receptors are also associated with developmental changes in catecholamine mediated cellular responses of ;pecific cells.Catecholamines are mediators of surfactant release (7) and smooth muscle tone in the mammalian lung. These effects are presumably the result of the interactions of adrenergic agonists with P-adrenergic receptors present on the plasma membranes of various pulmonary cells, resulting in the stimulation of adenylate cyclase thus increasing intracellular 3',5' cyclic adenosine monophosphate (CAMP) (2, 17). Studies from this laboratory have recently demonstrated that pulmonary /3-adrenergic receptors in the rat and rabbit increase dramatically during late gestation and during the suckling period, reaching adult levels by 28 days of postnatal age (26). Cheng et al. (5) have also recently demonstrated the ro...
SummaryThe present study was designed to describe the relationships among thyroid status, myocardial growth and myocardial P-adrenergic receptors in the developing rat ventricle. In normal rat myocardium the P-adrenergic binding capacity (B, , ) for (-)-I3HJ DHA decreased with increasing age and heart size. In order to determine the effect of thyroid status on ventricular growth characteristics and P-adrenergic receptors, animals were rendered: (1) hypothyroid with propylthiouracil (PTU), (2) euthyroid with PTU and daily thyroxine (T4) replacement, (3) hyperthyroid for several days with daily thyroxine injections or (4) normal controls with sham saline injections. Growth characteristics were similar in euthyroid and normal rat myocardium; ventricular weight, protein and DNA content were similar a t postnatal days 5, 15 and 28. Growth in hypothyroid pups was normal until postnatal day 14 a t which time the heart weight and protein content were significantly lower than in normal or euthyroid pups, whereas the number of P-adrenergic receptors was decreased in hypothyroid myocardium at all ages studied. On postnatal day 5 the (-)-I3HIDHA binding (B,,) was 37 a 9 in hypothyroid myocardium compared to 63 a 8 fmole per mg protein mean +-S.D. in euthyroid myocardium.The function of the P-adrenergic receptors was also decreased in hypothyroid as compared to euthyroid or normal myocardium a s demonstrated by a decrease in maximal catecholamine sensitive adenylate cyclase activity in myocardial membranes at 28 days of age. Treatment of hypothyroid or normal pups with T4 resulted in an increase in heart size, protein content and P-adrenergic receptors. Ventricular DNA content, which describes hyperplas& ---growth, was not decreased in hypothyroid rats demonstrating that postnatal hypertrophic but not hyperplastic ventricular growth is dependent on thyroid hormone. SpeculationThe decrease in P-adrenergic binding capacity in the rat ventricle during normal development is likely to reflect the decreasing proportion of sarcolemmal as compared to total ventricular proteins which occurs during hypertrophic growth. p-Adrenergic receptors are decreased in ventricles from hypothyroid rats a t all ages and the decreased production of cAMP in response to (-)-epinephrine in hypothyroid pups may relate to the decreased numbers of p-adrenergic receptors. Changes in thyroid status are highly associated with both P-adrenergic receptor status and the hypertrophic growth of the ventricular myocardium. We speculate that thyroid hormone is an important regulator of these changes during normal development.Catecholamines regulate cardiac rate and contractility by their interactions with adrenergic receptors present on sarcolemmal membranes. The effects of P-adrenergic agonists on cardiac function are dependent upon the stimulation of the enzyme adenylate cyclase which increases intracellular 3', 5' cyclic adenosine monophosphate (CAMP). P-Adrenergic responses and receptors have been identified in the mammalian myocardium early in developmen...
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