Katz M S, Kelly T M, Dax E M, Pineyro M A, Partilla J S, Gregerman R I
J Clin Endocrinol Metab. 1985 May;60(5):900-9. doi: 10.1210/jcem-60-5-900.
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.
大鼠肾上腺皮质癌的腺苷酸环化酶不仅可被促肾上腺皮质激素（ACTH）激活，还可被β-肾上腺素能激动剂激活，这些激动剂与正常大鼠肾上腺皮质中不存在的异位β-肾上腺素能受体结合。先前关于人类肾上腺皮质癌中腺苷酸环化酶可能受β-肾上腺素能控制的报道未能证明β-肾上腺素能受体相关的酶活性。我们研究了6例人类肾上腺皮质癌以及来自3名受试者的正常肾上腺皮质中的β-肾上腺素能激动剂敏感性腺苷酸环化酶和β-肾上腺素能结合位点。6例癌组织中有3例对ACTH和β-激动剂均有腺苷酸环化酶反应。2例肿瘤对ACTH有反应，但对β-激动剂无反应；1例肿瘤对β-激动剂有反应，但对ACTH无反应。3名受试者正常肾上腺皮质的腺苷酸环化酶活性可被ACTH刺激，但不能被β-激动剂刺激。在3例具有β-激动剂敏感性腺苷酸环化酶的肿瘤的膜制剂中，放射性标记的β-肾上腺素能拮抗剂[125I]吲哚洛尔特异性且高亲和力地（解离常数Kd = 38 - 83 pM）结合到一类单一的结合位点，该位点表现出配体浓度饱和、结合可逆性、药理学特异性和立体特异性。正常皮质和1例无β-肾上腺素能激动剂敏感性腺苷酸环化酶的肿瘤无[125I]吲哚洛尔的特异性结合。这些结果表明，人类肾上腺皮质的恶性转化常常但并非总是与功能上与腺苷酸环化酶相连的异位β-肾上腺素能受体的出现相关。ACTH反应性腺苷酸环化酶的丧失也可能与β-肾上腺素能受体相关的腺苷酸环化酶的发展同时发生。
