Human growth hormone-secreting pituitary adenoma cells in long-term culture: effects of dexamethasone and growth hormone releasing factor.
Growth hormone-secreting human pituitary adenoma cells in long-term culture show a decline in GH secretion. We investigated the effects of dexamethasone on GH production and on the responsiveness of the adenoma cells to various drugs. Twenty-four-hour GH secretion by cultures from seven acromegalics was consistently stimulated by 100 nM-dexamethasone. In four out of seven cultures the effect of dexamethasone occurred within 24 h. After 3 weeks in culture the decline in GH secretion by control cultures was over 90%, while in dexamethasone-treated cultures this was limited to less than 50%. The effect of dexamethasone was dose-dependent over a range of 1 nmol/l to 10 mumol/l. Dexamethasone stimulated not only GH secretion (fivefold), but also GH content (twofold). Cycloheximide and actinomycin D blocked the stimulatory effect of dexamethasone on GH secretion, the latter irreversibly. After 4 days of treatment with 100 nM-dexamethasone, the relative effects of somatostatin, prostaglandin E1, bromocriptine and thyrotrophin releasing hormone were the same in treated and untreated cultures. However, the response to synthetic GH releasing factor (GRF) was greatly enhanced by pretreatment of adenoma cells with dexamethasone (100 and 5 nmol/l). Cells unresponsive to small concentrations of GRF could be stimulated effectively by GRF after pretreatment with dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology
D003907:Dexamethasone; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone