ACTH and beta-endorphin secretion by three corticotrophic adenomas in culture. Effects of culture time, dexamethasone, vasopressin and synthetic corticotrophin releasing factor.
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 beta-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 beta-endorphin- LIR up to 8 h. Both the release of ACTH and beta-endorphin LIR were stimulated by 0.1 microM lysine vasopressin (LVP) in all three adenoma cell cultures. Dexamethasone (0.1 and 1 microM) suppressed basal hormone secretion for 4 h. Synthetic ovine corticotrophin-releasing factor (CRF) at 10 and 100 nM stimulated the secretion of ACTH and beta-endorphin LIR maximally. This stimulation was higher than observed with maximal stimulative concentration of LVP (0.3 microM). The CRF-mediated hormone secretion was calcium-dependent. Dexamethasone (0.1 microM) blocked the stimulating effect of 10 nM CRF completely. Gel-filtration chromatography demonstrated the cells to secrete both beta-lipotrophin (beta-LPH) and beta-endorphin. The ratio of beta-LPH to beta-endorphin released remained constant upon stimulation by LVP and CRF. HPLC studies demonstrate the possibility that several beta-endorphin fragments, including alpha-endorphin and gamma-endorphin, were secreted by cells from a Nelson tumour. CRF caused a simultaneous parallel stimulation of the release of these peptides.
D000236:Adenoma / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D002478:Cells, Cultured; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004723:Endorphins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008236:Lypressin / Q000494:pharmacology*; D009347:Nelson Syndrome / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D013997:Time Factors; D001615:beta-Endorphin
D004723:Endorphins; D008236:Lypressin; D001615:beta-Endorphin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone