Ontogeny of beta-adrenergic receptors in the rat lung: effects of hypothyroidism. 1982

J A Whitsett, and C Darovec-Beckerman, and J Pollinger, and J J Moore

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.

UI MeSH Term Description Entries
D007037 Hypothyroidism A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA. It may be primary or secondary due to other pituitary disease, or hypothalamic dysfunction. Central Hypothyroidism,Primary Hypothyroidism,Secondary Hypothyroidism,TSH Deficiency,Thyroid-Stimulating Hormone Deficiency,Central Hypothyroidisms,Deficiency, TSH,Deficiency, Thyroid-Stimulating Hormone,Hormone Deficiency, Thyroid-Stimulating,Hypothyroidism, Central,Hypothyroidism, Primary,Hypothyroidism, Secondary,Hypothyroidisms,Primary Hypothyroidisms,Secondary Hypothyroidisms,TSH Deficiencies,Thyroid Stimulating Hormone Deficiency,Thyroid-Stimulating Hormone Deficiencies
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011441 Propylthiouracil A thiourea antithyroid agent. Propythiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to tri-iodothyronine. It is used in the treatment of hyperthyroidism. (From Martindale, The Extra Pharmacopeoia, 30th ed, p534) 6-Propyl-2-Thiouracil,6 Propyl 2 Thiouracil
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011941 Receptors, Adrenergic Cell-surface proteins that bind epinephrine and/or norepinephrine with high affinity and trigger intracellular changes. The two major classes of adrenergic receptors, alpha and beta, were originally discriminated based on their cellular actions but now are distinguished by their relative affinity for characteristic synthetic ligands. Adrenergic receptors may also be classified according to the subtypes of G-proteins with which they bind; this scheme does not respect the alpha-beta distinction. Adrenergic Receptors,Adrenoceptor,Adrenoceptors,Norepinephrine Receptor,Receptors, Epinephrine,Receptors, Norepinephrine,Adrenergic Receptor,Epinephrine Receptors,Norepinephrine Receptors,Receptor, Adrenergic,Receptor, Norepinephrine
D011943 Receptors, Adrenergic, beta One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS. Adrenergic beta-Receptor,Adrenergic beta-Receptors,Receptors, beta-Adrenergic,beta Adrenergic Receptor,beta-Adrenergic Receptor,beta-Adrenergic Receptors,Receptor, Adrenergic, beta,Adrenergic Receptor, beta,Adrenergic beta Receptor,Adrenergic beta Receptors,Receptor, beta Adrenergic,Receptor, beta-Adrenergic,Receptors, beta Adrenergic,beta Adrenergic Receptors,beta-Receptor, Adrenergic,beta-Receptors, Adrenergic
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013974 Thyroxine The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism. L-Thyroxine,Levothyroxine,T4 Thyroid Hormone,3,5,3',5'-Tetraiodothyronine,Berlthyrox,Dexnon,Eferox,Eltroxin,Eltroxine,Euthyrox,Eutirox,L-3,5,3',5'-Tetraiodothyronine,L-Thyrox,L-Thyroxin Henning,L-Thyroxin beta,L-Thyroxine Roche,Levo-T,Levothroid,Levothyroid,Levothyroxin Deladande,Levothyroxin Delalande,Levothyroxine Sodium,Levoxine,Levoxyl,Lévothyrox,Novothyral,Novothyrox,O-(4-Hydroxy-3,5-diiodophenyl) 3,5-diiodo-L-tyrosine,O-(4-Hydroxy-3,5-diiodophenyl)-3,5-diiodotyrosine,Oroxine,Sodium Levothyroxine,Synthroid,Synthrox,Thevier,Thyrax,Thyroxin,Tiroidine,Tiroxina Leo,Unithroid,L Thyrox,L Thyroxin Henning,L Thyroxin beta,L Thyroxine,L Thyroxine Roche,Levo T,Thyroid Hormone, T4

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