Decreased myocardial adenyl cyclase activity in hypothyroidism

Abstract

A B S T R A C T It has been suggested that hypothyroidism may alter the responsiveness of the heart to sympathetic stimulation. To define more precisely the interrelationship between hypothyroidism and catecholamine responsiveness we: (a) studied the effects of norepinephrine and fluoride on the activation of adenyl cyclase in the particulate fraction of heart homogenates from euthyroid and hypothyroid cats; and (b) assessed the contractile response of isolated right ventricular papillary muscles from the same cats to increasing concentrations of norepinephrine. It was found that maximal accumulation of cyclic 3',5'-adenosine monophosphate (3',5'-AMP) was significantly lower at peak norepinephrine concentrations in the hypothyroid (284 ±5 pmoles) than in the euthyroid group (326 ±10 pmoles) (P < 0.02). However, the Km for norepinephrine was similar in both groups (1-2 X 10' moles/liter), and there was no apparent change in the threshold concentration. Fluoride-mediated increases in Cyclic 3',5'-AMP accumulation were also significantly lower in the hypothyroid (585 +25 pmoles) as compared to the euthyroid group (790 ±20 pmoles) (P < 0.02). In contrast, norepinephrine produced a similar augmentation of contractility in isolated papillary muscles from the hypothyroid and euthyroid cats. It thus appears that although the hypothyroid state is associated with a decrease in the total amount of myocardial adenyl cyclase per milligram of tissue capable of being activated by norepinephrine or fluoride, there is no change in the sensitivity of the enzyme to norepinephrine stimulation. Moreover, the finding that the inotropic response to norepinephrine is unaltered in hypothyroidism is compatible with the hypothesis that only a fraction of the total intracellular cyclic 3',5'-AMP produced by norepinephrine activation of adenyl cyclase is required to elicit the inotropic response.

Hypothyroidism Elicits Electrophysiological Noradrenergic Subsensitivity in Rat Cerebellum

“…In fact, diminished 1-receptor binding (with no change in affinity) during hypothyroidism has been demonstrated (3,15). In peripheral tissues, parallel changes in adenylate cyclase activity have been reported (16). Our electrophysiological studies agree well with previous observations (3,6,15,16).…”

The Influence of Hyperthyroidism and Hypothyroidism on the β-Adrenergic Responsiveness of the Turkey Erythrocyte

“…In contrast to hyperthyroidism, however, the means by which adrenergic responsiveness is (38)(39)(40). These results suggest that one mechanism for decreased adrenergic responsiveness in hypothyroidism common to many systems may be a reduction in the number of 8-receptors.…”

Plasma Adenosine 3′:5′-Cyclic Monophosphate Response to Glucagon in Thyroid Disease

“…It has been suggested that some of the metabolic abnormalities in thyroid disease may be secondary to alterations in the metabolism of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in tissues (Krishna, Hynie & Brodie, 1968;Levey, Skelton & Epstein, 1969a;Caldwell & Fain, 1971). Investigations of this type have largely been concerned with heart and adipose tissue of experimental animals, although metabolic changes have also been studied in the liver in thyroid disease (Freedland, 1965;Dooner, Parada, Aliaga & Hoyl, 1967;Klion, Segal & Schaffner, 1971).…”