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Modulatory Effect of Thyroid Function on Enzymes of the Vasopressin-Sensitive Adenosine 3',5'-Monophosphate System in Renal Medulla^*

THOMAS M. HARKCOM, JIN K. KIM, P. J. PALUMBO, YVONNE S. F. HUI and THOMAS P. DOUSA

Mayo Clinic and Mayo Foundation, and the Mayo Medical School Rochester, Minnesota 55901

Address all correspondence and requests for reprints to: T. P. Dousa, Mayo Clinic, 200 First Street S.W., Rochester, Minnesota 55901.

Abstract

Enzymes of hormone-dependent cAMP metabolism and other enzymes were studied in renal medulla, cortex, and liver of hypothyroid rats and of hypothyroid rats treated for 1 week with T₄.

In the hypothyroid group, basal activity of renal medullary adenylate cyclase and the activity stimulated by vasopressin were markedly decreased. Treatment of hypothyroid rats with T₄ resulted in an increase in the renal medullary adenylate cyclase activity and in a decrease of the activity of cAMP phosphodiesterase. In studies of other renal medullary enzymes, only cytochrome c oxidase activity was decreased in hypothyroidism, but it was not influenced by T₄ treatment. In vitro, the addition of 10^-7-10^-5 M T₄ had no effect on adenylate cyclase activity or on its stimulation by vasopressin or NaF. At 10-5 M, but not at lower concentrations, T₄ inhibited cAMP phosphodiesterase. The activity of cAMP-dependent protein kinase in cytosol was not different among the three groups, but the state of activation of protein kinase in situ was lower in hypothyroid rats. The responsiveness of renal cortical adenylate cyclase to parathyroid hormone was markedly diminished in hypothyroid rats and was not influenced by T₄ treatment. On the other hand, basal, NaF-stimulated, and 5'- guanylylimidodiphosphate-stimulated activity of renal cortical adenylate cyclase did not depend on the thyroid state. Hepatic adenylate cyclase activity was not decreased in the hypothyroid state and was increased by T₄ treatment. Hypothyroid rats had higher, and T₄- treated rats had lower, urinary volume than euthyroid controls.

These results indicate that thyroid hormones have a specific modulatory effect on the vasopressin-responsive adenylate cyclase-cAMP system in the renal medulla and suggest that thyroid hormones may influence cellular action of vasopressin in the renal medulla at the site of vasopressin-dependent cAMP formation. (Endocrinology 102: 1475, 1978)

Footnotes

^* This study was supported by USPHS Research Grant AM-16105 from NIAMDD and by a Grant-in-Aid from the AHA, with funds contributed in part by the Minnesota Heart Association, the Northwest Area Foundation, and the Mayo Foundation. The results of this study were presented in part at the National Meeting of the American Federation for Clinical Research in Atlantic City, NJ, May, 1976 (Clin Res 24: 401A, 1976).

Student of the Mayo Medical School.

Postdoctoral fellow of the Minnesota Heart Association.

Established Investigator of the AMA.

Received February 3, 1977.

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