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Multiple Specific Hormone Receptors in the Adenylate Cyclase of an Adrenocortical Carcinoma

1971; Elsevier BV; Volume: 246; Issue: 18 Linguagem: Inglês

10.1016/s0021-9258(18)61876-9

1083-351X

Immanuel Schorr, P. Rathnam, B.B. Saxena, Robert L. Ney,

Cancer, Hypoxia, and Metabolism

Abstract The adenylate cyclase of a corticosterone producing transplanted adrenal cancer of the rat is stimulated not only by adrenocorticotropic hormone (ACTH), but also by epinephrine, norepinephrine, thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone. The lowest effective concentration of each hormone is about 10-6 m. Other hormones, including parathyroid hormone, thyrocalcitonin, glucagon, and vasopressin, do not influence the tumor cyclase. ACTH is the only hormone that stimulates normal adrenal adenylate cyclase. To study further the characteristics of the tumor hormone receptors, experiments have been performed employing hormone analogues, subunits, and inhibitors. The tumor ACTH receptor requires similar portions of the ACTH molecule for activity as does the normal adrenal receptor. Thus, the tumor and the normal adrenal cyclase are stimulated by the ACTH analogue containing the NH2-terminal 24 amino acids of ACTH, but neither responds to the analogue containing only the COOH-terminal 15 amino acids. A number of observations suggest that the tumor possesses a β adrenergic receptor. The tumor cyclase is stimulated by a series of catecholamines in the following order of potency: isoproterenol g epinephrine g norepinephrine g ephedrine. Methoxamine is inactive. The β adrenergic antagonist propranolol abolishes the stimulatory effect of the catecholamines but not that of the other hormones. Phentolamine and dibenzylamine do not block the catecholamine responses. Studies with the subunits of luteinizing hormone and follicle-stimulating hormone have shown activity in stimulating the tumor cyclase principally by the β subunit of each hormone. The results indicate the presence of multiple specific hormone receptors in the tumor cyclase. Since the effects of the different hormones are not additive, it is suggested that the multiple hormone receptors act through a common cyclase catalytic unit.