Tumor tissues obtained from two patients with the
ectopic ACTH syndrome caused by
medullary carcinoma of the thyroid and malignant epithelial
thymoma were dispersed by tryptic digestion and mechanical agitation. Using the isolated cells, the effects of various agents on
ACTH secretion and intracellular cAMP concentrations were studied. Addition of rat median eminence extract significantly stimulated
ACTH secretion and increased levels of intracellular cAMP in both cell preparations, and a dose-response relationship appeared to exist between the dose of rat median eminence extract added and either
ACTH secretion or intracellular cAMP formation in the
thymic tumor cells. High concentrations of
calcium also produced a marked
ACTH secretion in both cases. In the
thymic tumor cells,
norepinephrine,
serotonin, and TRH were found to be effective in increasing
ACTH secretion and intracellular cAMP levels, whereas
biogenic amines,
hypothalamic hormones, and
gastrointestinal hormones did not affect
hormone secretion in the thyroid
tumor cells. These results suggest that a corticortropin-releasing factor-like
substance(s), as yet unspecified, may play some role in stimulating ectopic
ACTH secretion by certain
tumors, that both intracellular cAMP and Ca++ may be involved in
ectopic hormone secretion, and that the inappropriate hormonal secretory responses of some
tumors to a variety of stimuli might be mediated by altered membrane receptors of the neoplastic cells.