Clinical Studies On The Influence Of Endogenous Opioid Peptides In Acth Secretion

We have used the serum N-POMC level as indication of ACTH secretion to test the effects of a low (0.4mg) and a high (16mg) dose of naloxone on the basal secretion oi ACTH and cortisol in normal subjects and patients with pituitary-adrenal disorders; to test the effect of naloxone on the responses of ACTH and cortisol to oCRH in seven patients with Cushing's disease and six normal subjects as controls; and to test the effect of naloxone on the release of ACTH stimulated by insulin—induced hypoglycemia in five normal subjects and five patients with Cushing's disease.Results:(1) In eight normal subjects the high dose of naloxone caused obvious increases in serum N-POMC and cortisol concentrations at 30, 60 and 90 minute (p < 0.02-0.001) compared with that after injection of 0.9% saline, whereas the low dose of naloxone was ineffective. Similar response of blood N-POMC, not cortisol, to high dose of naloxone was found in five patients with Addison's disease and four patients with conjenital adrenal hyperplasia. But both doses of naloxone failed to influence blood N-POMC and cortisol levels in eight patients with ACTH-dependent Cushing's disease or Nelson's syndrome. These results suggest that inhibitory δ- or κ-opiate receptors (insensitive to naloxone) are involved in the regulation of ACTH secretion. In patients with Cusing's disease or Nelson's syndrome ACTH is not altered by naloxone.(2). The peak values of serum N-POMC after intravenous injection of oCRH1-41(100ug) in controls and patients with Cushing's disease rose 2.0 ± 0.2 and2.0± 0.3 folds respectively which were not different from each other (p > 0.9), and the peak levels of plasma cortisol increased to the same extent as serum N-POMC which were 2.2 ± 0.4 and 1.6 ± 0.2 folds of their basal levels respectively. These results reflect that exogenous CRH can stimulate N-POMC and cortisol secretion both in normal subjects and patients with Cushing's disease. However, the additional injection of naloxone (25 mg) could cause further increases of blood N—POMC and cortisol only in normal subjects, but not in patients with Cushing's disease. Naloxone, by blooking the inhibitory effect of opioid peptides on CRH secretion, might cause an increase of N-POMC and cortisol in normal subjects.(3). In normal subjects, insulin-induced hypoglycemia (0.15 u / kg) caused prompt increases in blood N-POMC and cortisol levels. The peak changes (peak values minus basal values) of N—POMC and cortisol during insulin— induced hypoglycemia were 777 ± 127 pg/ ml and 17.6± 1.5 ug/ dl respectively, which were unchanged by the additional injection of naloxone (25 mg). The effects of naloxone and insulin were not addictive. Thse results indicate that naloxone and the hypoglycemia—stress stimulated release of ACTH may act, at least in part, through common mechanisms, that is, through disinhibition of opiate inhibition on pituitary—adrenal axis. But in patients with Cushing's disease, both insulin—induced hypoglycemia (0.30 u/ kg) and naloxone could not alter the blood...