β-Adrenergic Receptors and Catecholamine Sensitive Adenylate Cyclase in Developing Rat Ventricular Myocardium: Effect of Thyroid Status

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Abstract
Summary: The present study was designed to describe the relationships among thyroid status, myocardial growth and myocardial β-adrenergic receptors in the developing rat ventricle. In normal rat myocardium the β-adrenergic binding capacity (Bmax) for (-)-[3H] DHA decreased with increasing age and heart size. In order to determine the effect of thyroid status on ventricular growth characteristics and β-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 at postnatal days 5, 15 and 28. Growth in hypothyroid pups was normal until postnatal day 14 at which time the heart weight and protein content were significantly lower than in normal or euthyroid pups, whereas the number of β-adrenergic receptors was decreased in hypothyroid myocardium at all ages studied. On postnatal day 5 the (–)-[3H]DHA binding (Bmax) was 37 ± 9 in hypothyroid myocardium compared to 63 ± 8 fmole per mg protein mean ± S.D. in euthyroid myocardium. The function of the β-adrenergic receptors was also decreased in hypothyroid as compared to euthyroid or normal myocardium as 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 β-adrenergic receptors. Ventricular DNA content, which describes hyperplastic growth, was not decreased in hypothyroid rats demonstrating that postnatal hypertrophic but not hyperplastic ventricular growth is dependent on thyroid hormone. Speculation: The decrease in β-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. β-Adrenergic receptors are decreased in ventricles from hypothyroid rats at all ages and the decreased production of cAMP in response to (-)- epinephrine in hypothyroid pups may relate to the decreased numbers of β-adrenergic receptors. Changes in thyroid status are highly associated with both β-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.