Glucocorticoids stimulate the production of preprocalcitonin-derived secretory peptides by a rat medullary thyroid carcinoma cell line.
A rat medullary thyroid carcinoma cell line, CA-77, has been established as a model system for investigating calcitonin biosynthesis and secretion. Growth of this cell line in serum-free defined medium provided suitable conditions for studying steroid hormone effects on the production of calcitonin and related peptides. After exposure for 5 days to a variety of steroids, only dexamethasone and corticosterone increased cellular content of calcitonin and a second secretory peptide (CCAP) derived from the same mRNA translation product as calcitonin. Glucocorticoids had no effect on cellular somatostatin, another secretory product of these cells. Increasing doses of dexamethasone progressively elevated cellular calcitonin and CCAP, with a maximal effect at 10(-8) M; 10(-9) M and lower doses were ineffective. On a molar basis, corticosterone was approximately 50-fold less potent than the synthetic glucocorticoid. An increase in cellular calcitonin content was observed only after 48 h of glucocorticoid treatment; a maximum increase (13-fold) occurred after 7 days. Glucocorticoids also increased basal calcitonin secretion. Similar effects were observed for cellular and secreted CCAP. Withdrawal of dexamethasone after 4 days of treatment lowered cellular calcitonin toward the level of control cultures. Dexamethasone pretreatment potentiated the acute secretory response to calcium for both calcitonin and CCAP, while no such enhancement was noted for calcium stimulation of somatostatin secretion. We conclude that the glucocorticoids specifically stimulate the production and secretion of calcitonin and CCAP, two secretory peptides derived from preprocalcitonin.
D000818:Animals; D002116:Calcitonin / Q000235:genetics*; D002117:Calcitriol / Q000494:pharmacology; D002460:Cell Line; D002762:Cholecalciferol / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D007700:Kinetics; D010446:Peptide Fragments / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D011863:Radioimmunoassay; D051381:Rats; D013964:Thyroid Neoplasms / Q000378:metabolism*
D010446:Peptide Fragments; D011498:Protein Precursors; D013196:Dihydrotestosterone; D002762:Cholecalciferol; D004958:Estradiol; D003907:Dexamethasone; C033183:preprocalcitonin; C037553:katacalcin; D002116:Calcitonin; D002117:Calcitriol; D003345:Corticosterone