Ectopic β-Adrenergic Receptors Coupled to Adenylate Cyclase in Human Adrenocortical Carcinomas

Michael S. Katz, Thomas M. Kelly, Elizabeth M. Dax, Marco A. Pineyro, John S. Partilla, Robert I. Gregerman

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

The adenylate cyclase of an adrenocortical carcinoma of the rat is activated not only by ACTH but also by β-adrenergic agonists, which bind to ectopic β-adrenergic receptors not present in normal rat adrenal cortex. Previous reports examining possible β-adrenergic control of adenylate cyclase in human adrenocortical carcinomas failed to demonstrate β-adrenergic receptor-linked enzyme activity. We studied six human adrenal carcinomas and normal adrenal cortex from three subjects for β-adrenergic agonist-sensitive adenylate cyclase and β-adrenergic binding sites. Three of the six carcinomas had ade-nylate cyclase responses to both ACTH and β-agonists. Two tumors were ACTH responsive but not β3-agonist responsive; one tumor responded to β-agonists but not to ACTH. Adenylate cyclase activity of normal adrenal cortex from three subjects was stimulated by ACTH but not by β3-agonists. In membrane prep-arations from three tumors with β-agonist-sensitive adenylate cyclase, the radiolabeled β-adrenergic antagonist [125I]pindolol bound specifically and with high affinity (Kd = 38-83 pM) to single class of binding sites which showed saturation with ligand concentration, reversibility of binding, pharmacological specificity, and stereospecificity. Normal cortex and one tumor without β-adrenergic agonist-sensitive adenylate cyclase had no specific binding of [125I]pindolol. These results indicate that malignant transformation of adrenal cortex in man is frequently but not invariably associated with the appearance of ectopic β-adrenergic receptors functionally linked to adenylate cyclase. Loss of ACTH-responsive adenylate cyclase may also occur simultaneously with the development of β-adrenergic receptor-linked ad-enylate cyclase.

Original languageEnglish (US)
Pages (from-to)900-909
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume60
Issue number5
DOIs
StatePublished - May 1985

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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