Hypothyroidism modulates beta adrenergic receptor adenylate cyclase interactions in rat reticulocytes.

Stiles, Gary L.; Stadel, Jeffrey M.; Léan, André De; Lefkowitz, Robert J.

doi:10.1172/jci110397

Cited by 54 publications

(13 citation statements)

References 13 publications

(13 reference statements)

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“…Reticulocytes from hypothyroid rats, like the hypothyroid turkey erythrocytes described in the preceding section, have a reduction in /3 receptor number of approximately 50% (68). Although the K d for the radioligand [ 3 H]DHA is unchanged (68), it has been reported that there is a reduction in overall binding affinity for isoproterenol attributable to changes in the selective binding affinities of sites in both high-and lowaffinity states (68).…”

Section: Beta Receptorsmentioning

confidence: 87%

The Influence of Hyperthyroidism and Hypothyroidism on α and β-Adrenergic Receptor Systems and Adrenergic Responsiveness*

1983

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A detailed review has been conducted of studies addressing dressing the subject of the influence of thyroid hormone on alpha- and beta-adrenergic receptors and adrenergic responsiveness in a wide range of experimental animals and tissues. The studies summarized in the present article have been restricted to those in which explicit measurements of receptor number were made by the use of appropriate radioligands. Particular emphasis is given to an examination of the relationship between thyroid hormone-induced changes in alpha- and beta-adrenergic receptor number and accompanying changes in adenylate cyclase activity and more distal adrenergic responses. Although in many instances thyroid hormone-induced changes in receptor number are reflected in coordinate changes in adrenergic sensitivity, this is shown to be by no means uniformly the case. In contrasting instances, modifications at other more distal sites in the sequence of events mediating catecholamine hormone action are responsible for biochemical and physiological changes in catecholamine responsiveness induced by thyroid hormone.

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Section: Beta Receptorsmentioning

confidence: 87%

The Influence of Hyperthyroidism and Hypothyroidism on α and β-Adrenergic Receptor Systems and Adrenergic Responsiveness*

1983

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“…Rat adipose tissue BAR have been said to be unchanged in hyperthyroid states [15], and liver BAR decreased [22]. Conversely, the hypothyroid state is generally associated with reductions in BAR density in heart [6], turkey erythrocytes [3], rat reticulocytes [31], cortex [16] and cerebellum [29].…”

Section: Discussionmentioning

confidence: 99%

Effect of Thyroid Status on Lung and Heart Beta-Adrenergic Receptors in Fetal and Newborn Sheep

Padbury¹,

Klein²,

Polk³

et al. 1986

Dev Pharmacol Ther

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The effect of altered thyroid status on the development of beta-adrenergic receptor (BAR) density and affinity was investigated in ovine fetal and newborn heart and lung. Fetal (119-121 days gestation) and newborn (2-3 days of age) sheep underwent either thyroidectomy alone, thyroidectomy plus infusion of a large dose of T3 or sham operation. Eight days later BAR were measured in heart and lung using the tritiated radioligand dihydroalprenolol. There was no apparent effect of altered thyroid status on fetal heart or lung BAR density or affinity. In contrast, the newborns thyroidectomized and infused with T3 had a 96% increase in heart BAR density and an 83% increase in lung BAR compared to the thyroidectomized only or sham-operated newborns which were similar. These results suggest that in the near term ovine fetus heart and lung tissue BAR are neither dependent on nor responsive to thyroid hormones, whereas in the newborn period heart and lung BAR are highly responsive to thyroid hormones.

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“…In other situations where N is genetically deficient, such as the cyc-variant of S49 lymphoma cells (22), or in situations where there is uncoupling of R from N such as desensitization (35), hypothyroidism (36), or hypoadrenalism (37), there is a reduction in the agonist-specific high affinity binding component that is demonstrated by a right-shifted and steepened agonist competition curve. This was precisely the situation documented in this study for the competition curves of the PHP-Ia patients.…”

Section: Resultsmentioning

confidence: 99%

Impaired formation of beta-adrenergic receptor-nucleotide regulatory protein complexes in pseudohypoparathyroidism.

Heinsimer¹,

Davies²,

Downs³

et al. 1984

J. Clin. Invest.

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Abstract. Decreased activity ofthe guanine nucleotide regulatory protein (N) of the adenylate cyclase system is present in cell membranes ofsome patients with pseudohypoparathyrodism (PHP-Ia) whereas others have normal activity of N (PHP-Ib). Low N activity in PHPIa results in a decrease in hormone (H)-stimulatable adenylate cyclase in various tissues, which might be due to decreased ability to form an agonist-specific high affinity complex composed of H, receptor (R), and N. To test this hypothesis, we compared f3-adrenergic agonist-specific binding properties in erythrocyte membranes from five patients with PHP-Ia (N = 45% of control), five patients with PHP-Ib (N = 97%), and five control subjects. Competition curves that were generated by increasing concentrations ofthe (3-agonist isoproterenol competing with ['251]pindolol were shallow (slope factors < 1) and were computer fit to a two-state model with corresponding high and low affinity for the agonist. The agonist competition curves from the PHP-Ia patients were shifted significantly (P < 0.02) to the right as a result of a significant (P < 0.01) decrease in the percent of fl-adrenergic receptors in the high affinity state from 64±22% in PHPIb and 56±5% in controls to 10±8% in PHP-Ia. The agonist competition curves were computer fit to a "ternary These in vitro findings in erythrocytes taken together with the recent observations that in vivo isoproterenolstimulated adenylate cyclase activity is decreased in patients with PHP (Carlson, H. E., and A. S. Brickman, 1983, J. Clin. Endocrinol. Metab. 56:1323-1326 are consistent with the notion that N is a bifunctional protein interacting with both R and the adenylate cyclase. It may be that in patients with PHP-Ia a single molecular and genetic defect accounts for both decreased HRN formation and decreased adenylate cyclase activity, whereas in PHP-Ib the biochemical lesion(s) appear not to affect HRN complex formation.

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Hypothyroidism modulates beta adrenergic receptor adenylate cyclase interactions in rat reticulocytes.

Cited by 54 publications

References 13 publications

The Influence of Hyperthyroidism and Hypothyroidism on α and β-Adrenergic Receptor Systems and Adrenergic Responsiveness*

The Influence of Hyperthyroidism and Hypothyroidism on α and β-Adrenergic Receptor Systems and Adrenergic Responsiveness*

Effect of Thyroid Status on Lung and Heart Beta-Adrenergic Receptors in Fetal and Newborn Sheep

Impaired formation of beta-adrenergic receptor-nucleotide regulatory protein complexes in pseudohypoparathyroidism.

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