The role of endogenous opioid receptors on anterior pituitary hormone secretion was evaluated by the administration of the opioid receptor antagonist naloxone. The infusion of naloxone (8 mg iv followed by 4 mg/h for 3 h) did not alter basal growth hormone (GH), prolactin (Prl) and thyrotrophin (TSH) secretion but produced a significant rise in cortisol and gonadotrophins in normal man. The infusion of the opiate antagonist appeared to increase the rate and amplitude of luteinizing hormone (LH) pulsatility. Naloxone pre-medication (10 mg iv 30 min before testing) did not alter the pituitary response to TRH and LRH stimulation.These results demonstrate that naloxone can modify basal anterior pituitary hormone secretion and strongly suggest an endogenous opioid modulation of some of these hormones.It has been long known that morphine and related compounds can influence pituitary hormone secre¬ tion by virtue of action on the central nervous system (Meites et al. 1979). The recent discovery of opiate receptors in the brain of mammals as well as the isolation of endogenous opioid-like substances (Hughes et al. 1975), has led to considerable spe¬ culation regarding their physiological role in the control of the hypothalamus-pituitary-axis. Exogenously administered endorphins and enkephalins have been shown to affect pituitary hormone secre¬ tion in experimental animals (Bruni et al. 1977) and the reversal or attenuation of the effect by naloxone, an opiate antagonist, is taken as neuropharmacological evidence for the involvement of opiate receptors in this process.In man, morphine raised basal prolactin (Prl) levels, but did not alter basal growth hormone (GH) and cortisol secretion (Tolis et al. 1975), whereas a long-acting analogue of met-enkephalin released Prl, GH and decreased gonadotrophins and cortisol (Von Graffenried et al. 1978; Stubbs et al. 1978). The prior administration of naloxone blunted these effects (Stubbs et al. 1978).To further investigate the role of opiate recep¬ tors and, possibly, identify an action of endogenous opiate receptors on anterior pituitary function, we have studied the effect of naloxone, a potent opiate antagonist compound, on basal and TRH/LRH stimulated pituitary hormone secretion in man. Materials and Methods Naloxone infusionSix normal males, aged 20-38 years, were studied fast¬ ing and single (subject) blind. Each subject was tested on two different days, the two treatments being given in random order at least 7 days apart. Starting at 08.30 h, an iv cannula was inserted in an antecubital vein for blood sampling and kept patent with 0.9% saline. A second iv cannula was placed in the opposite arm for the infusion of 0.9% saline or naloxone (Naloxone HC1, Endo Labo¬ ratories, Inc., New York, USA). Thirty min after cannuladon, half hourly sampling was started for 420 min.
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