ACTH and β-endorphin secretion by three corticotrophic adenomas in culture. Effects of culture time, dexamethasone, vasopressin and synthetic corticotrophin releasing factor

Abstract

Abstract. Dispersed corticotrophic cells of 3 patients with Nelson's syndrome were studied in tissue culture for up to 25 days. During this culture period a parallel decrease with time was seen in ACTH and β-endorphin-like immunoreactivity (LIR) release. A concomitant decline was observed for intracellular hormones. The time course of hormone release showed a parallel secretion of ACTH and β-endorphin-LIR up to 8 h. Both the release of ACTH and β-endorphin LIR were stimulated by 0.1 μm lysine vasopressin (LVP) in all three adenoma cell cultures. Dexamethasone (0.1 and 1 μm) suppressed basal hormone secretion for 4 h. Synthetic ovine corticotrophin-releasing factor (CRF) at 10 and 100 nm stimulated the secretion of ACTH and β-endorphin LIR maximally. This stimulation was higher than observed with maximal stimulative concentration of LVP (0.3 μm). The CRF-mediated hormone secretion was calcium-dependent. Dexamethasone (0.1 μm) blocked the stimulating effect of 10 nm CRF completely. Gel-filtration chromatography demonstrated the cells to secrete both β-lipotrophin (β-LPH) and β-endorphin. The ratio of β-LPH to β-endorphin released remained constant upon stimulation by LVP and CRF. HPLC studies demonstrate the possibility that several β-endorphin fragments, including α-endorphin and γ-endorphin, were secreted by cells from a Nelson tumour. CRF caused a simultaneous parallel stimulation of the release of these peptides.