Secretion of adrenocorticotropin, β -endorphin and calcitonin by cultured medullary thyroid carcinoma cells. Effects of synthetic corticotropin-releasing factor and lysine vasopressin

Abstract

Abstract. The present study was performed to investigate the potential of human medullary thyroid carcinoma (MTC) cells to secrete ACTH, β-LPH/β-EP. In addition, these studies might shed further light on the possible synthesis of a common precursor molecule for calcitonin (CT), ACTH and β-LPH/β-EP. MTC tissue was obtained from 10 patients (6 familial, 4 sporadic) without clinical and biochemical signs of Cushing's syndrome. Single cell suspensions were cultured for 1 to 2 weeks. Mean basal release of β-LPH/β-EP was 0.76 ± 0.29 (se) ng/106 cells/4 h (n = 10). Dibutyryl cyclic AMP (3 mm) stimulated β-EP release significantly in 3 out of 7 cultures, while Ca2+ (2 mm) had no effect at all. The effects of the physiological regulators of pituitary ACTH and β-LPH/β-EP secretion, synthetic corticotropin-releasing factor (CRF-41) and vasopressin (LVP) were also studied in these MTC cell cultures. LVP (100 nm) had no effect on β-EP release from MTC cells of all 8 cultures investigated. CRF-41 (10 nm) stimulated β-EP release from 5 cultures and was without effect on 4. Maximal stimulation was noticed with 10 nm, while the effect of 100 nm CRF-41 was lower or absent. Stimulation was most outspoken in 3 cultures of familial MTC, whereas in 2 cultures of sporadic MTC CRF-41 stimulated β-EP release marginally only after a 24 h incubation. LVP and/or CRF-41 stimulated CT release significantly in 3 cultures from sporadic MTC, while in these cultures the effect of CRF-41 on β-EP release was either very small or absent. LVP and CRF-41 did not stimulate CT release in 5 and 6 other cultures, respectively. In conclusion, no evidence was obtained for a concomitant secretion of β-EP and CT by MTC cells in culture. Synthetic ovine CRF-41, but not LVP is able to stimulate ACTH and β-EP release especially in cultures from patients with familial MTC, and CRF-41 and LVP stimulate CT release in cultures from some patients with sporadic MTC.