Beta-lipotropin/adrenocorticotropic hormone responses to corticotropin releasing hormone, hypoglycemia, metyrapone and dexamethasone in normal human subjects.

1. The possible correlation between secretions of adrenocorticotropic hormone (ACTH) and of beta-lipotropin (beta-LPH), two pro-opiomelanocortin (POMC)-derived peptides, was investigated in 27 normal subjects under basal conditions (circadian rhythm), after the administration of 1 mg dexamethasone and in tests involving acute (human corticotropin releasing hormone, hCRH, and insulin tolerance test, ITT) and chronic (metyrapone) stimulation. 2. All subjects presented circadian rhythm and an operating negative feedback mechanism. Plasma ACTH and beta-LPH concentrations were correlated in all tests. The increase in ACTH and beta-LPH levels after hCRH was lower than that detected after ITT, though both increases were more discrete than those detected after stimulation with metyrapone. 3. The data suggest that, under hypoglycemic conditions, ACTH and beta-LPH secretion involves other POMC secretagogues in addition to endogenous CRH. The nature of these factors remains undefined. The greater efficacy of metyrapone treatment in elevating ACTH and beta-LPH levels is most likely mediated by sustained reduction in cortisol production and interruption of the rapid steroid feedback on the pituitary. 4. The molar peak ratios of the acute tests, which were similar to one another, differed from the peak ratio obtained during the metyrapone test, suggesting that corticotrophs may present pools with differentiated ACTH and beta-LPH content and release according to the type and/or duration of the stimulus.