Adenyl Cyclase Activity in Tumorous Endocrine Tissues

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Since Schorr et al. first reported that a rat transplantable, corticosterone-producing adrenal carcinoma possessed not only a receptor for ACTH but also receptors for LH, FSH, TSH, epinephrine and norepinephrine, the aberrant adenyl cyclase response to multiple hormones have been studied in tumorous endocrine tissues of the rat and the human. In the present experiments, we investigated the adenyl cyclase responses of several endocrine tumors in human. The measurement of the adenyl cyclase activity was done based on the conversion of 8-14C-ATP to 14C-cyclic AMP during the incubation at 37° for 20min. of the whole tissue homogenate in the Tris buffer containing ATP regenerating system, ATP, MgSO4 and theophylline. In some experiments, slices of tumor tissue were incubated in vitro in Krebs-Ringer-bicarbonate-glucose medium containing hormones under 95% O2-5% CO2 at 37°. After incubation, the media were analysed for hormone released and the slices for the tissue cyclic AMP. Out of four pituitary adenomas from acromegalic patients, the adenyl cyclase reacted to TRH in two, LH-RH in two, dopamine in three, prostaglandin E1 in all and norepinephrine in three. It is noted that the positive responses of GH release in the patients after TRH or LH-RH loading before hypophysectomy coincidentally related to the adenyl cyclase activation in the same way by TRH or LH-RH, indicating that the GH release after nonspecific hypothalamic hormones given in the patients with acromegaly might be due to an alteration of the cellular membrane. This results in the binding of these pepides to an altered receptor and the activation of the adenyl cyclase system, The adenyl cyclase of an ectopic ACTH producing gastric carcinoid was activated by TRH, LH-RH, serotonin, nonepinephrine and median eminence extract of rat, which stimulated ACTH release into the incubation media in vitro. A medullary carcinoma of thyroid gland possessed adenyl cyclase system responsive to glucagon, TRH, epinephrine and norepinephrine. An activation by serotonin and suppression by calcitonin and high Ca++ were observed in a parathyroid adenoma adenyl cyclase system. Among four adrenal adenomas from patients with Cushing's syndrome, the adenyl cyclase was stimulated by TSH in two, by norepinephrine in two and by epinephrine in two other than ACTH. In two cases of aldosterone producing adrenal adenoma, the adenyl cyclase was stimulated by ACTH and prostaglandinE1 but not angiotensin II. The adenyl cyclase was responsive toglucagon in three pheochromocytoma but not in one. Glucagon induced hypertensive response was oberved in one patient tested with a positive adenyl cyclase response to glucagon, indicating that nonspecific glucagon receptor might be involved in the hypertensive reaction in pheochromocytoma. These results indicate that tumorous endocrine glands possess frequently nonspecific and inappropriate multiple hormone receptors. However, the physiological significance of these findings remains to be elucidated.
Japan Society of Clinical Chemistryの論文

Adenyl Cyclase Activity in Tumorous Endocrine Tissues

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