Ectopic β-Adrenergic Receptors Coupled to Adenylate Cyclase in Human Adrenocortical Carcinomas*
| Autor: | Elizabeth M. Dax, Michael S. Katz, Marco A. Pineyro, Thomas M. Kelly, Robert I. Gregerman, John S. Partilla |
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| Rok vydání: | 1985 |
| Předmět: |
Adult
Male medicine.medical_specialty Epinephrine Adrenergic receptor Endocrinology Diabetes and Metabolism Clinical Biochemistry Adrenal Gland Neoplasms Adenylate kinase Biology Binding Competitive Biochemistry Cyclase Norepinephrine chemistry.chemical_compound Endocrinology Adrenocorticotropic Hormone Internal medicine Receptors Adrenergic beta medicine Humans Adrenocortical carcinoma heterocyclic compounds Receptor Aged Adrenal cortex Prednimustine Biochemistry (medical) Isoproterenol Middle Aged medicine.disease medicine.anatomical_structure chemistry Pindolol Adrenal Cortex Female Cyclase activity Adenylyl Cyclases |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 60:900-909 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jcem-60-5-900 |
| Popis: | The adenylate cyclase of an adrenocortical carcinoma of the rat is activated not only by ACTH but also by beta-adrenergic agonists, which bind to ectopic beta-adrenergic receptors not present in normal rat adrenal cortex. Previous reports examining possible beta-adrenergic control of adenylate cyclase in human adrenocortical carcinomas failed to demonstrate beta-adrenergic receptor-linked enzyme activity. We studied six human adrenal carcinomas and normal adrenal cortex from three subjects for beta-adrenergic agonist-sensitive adenylate cyclase and beta-adrenergic binding sites. Three of the six carcinomas had adenylate cyclase responses to both ACTH and beta-agonists. Two tumors were ACTH responsive but not beta-agonist responsive; one tumor responded to beta-agonists but not to ACTH. Adenylate cyclase activity of normal adrenal cortex from three subjects was stimulated by ACTH but not by beta-agonists. In membrane preparations from three tumors with beta-agonist-sensitive adenylate cyclase, the radiolabeled beta-adrenergic antagonist [125I]pindolol bound specifically and with high affinity (Kd = 38-83 pM) to a single class of binding sites which showed saturation with ligand concentration, reversibility of binding, pharmacological specificity, and stereospecificity. Normal cortex and one tumor without beta-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 beta-adrenergic receptors functionally linked to adenylate cyclase. Loss of ACTH-responsive adenylate cyclase may also occur simultaneously with the development of beta-adrenergic receptor-linked adenylate cyclase. |
| Databáze: | OpenAIRE |
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