Opiate receptors and anterior pituitary hormone secretion in man. Effect of naloxone infusion

Abstract

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.

Morphine-Induced TSH Release in Normal and Hypothyroid Subjects

“…Contradictory data exist about the effects of naloxone on PRL and TSH secretion. Some au thors reported a decrease in TSH levels in normal human volunteers [12], other studies failed to show any effect both in normal [3,28] and hypothyroid subjects [13,28], Nalox one seems to have no effects on PRL secretion too [3,16,28], although a reduction in PRL serum levels has been re ported in human subjects [34] as observed in animals [2,41], The reason of these discrepancies is not clear.…”

Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man.

“…Moreover, the administration of opiate-receptor antagonists alone significantly amplifies the pulsatile mode of LH release, with attendant increases in the frequency and peak amplitude ofboth immunoactive and biologically active LH pulses (1 1-15). The ability of opiate-receptor antagonists to enhance episodic LH secretion in vivo (11)(12)(13)(14)(15) and to stimulate gonadotropin-releasing hormone (GnRH) secretion from human hypothalamic tissue in vitro (16,17) has suggested that the inhibitory action of endogenous opiates is exerted at the level of the hypothalamic pulse generator for GnRH.…”

The Effects of Endogenous Opioids and Cortisol on Thyrotropin and Prolactin Secretion in Patients with Addison’s Disease1

“…The acute administration of opioid peptides may have no effect (8), may inhibit (9), or may increase (2, 10 -13) basal or TRH-stimulated TSH release. Moreover, several studies have found that naloxone, in doses up to 20 mg, had no effect on basal and stimulated TSH secretion (1,5,14,15), whereas other authors have found a decrease in basal TSH secretion (11, 16) or a blunted TSH response to TRH or exogenous opiates (16, 17) in normal subjects.In a recent study (18), we found a dose-dependent inhibitory action of cortisol on TSH secretion in Addison patients (18). Our results suggested a glucocorticoid-mediated suppression of the pituitary sensitivity to TRH, although a synergistic effect at the hypothalamic level could not be excluded.…”

“…Although exogenous opioid peptides consistently increase the secretion of PRL (8,10,12), conflicting results concerning the effects of naloxone on PRL release have been published. Most studies have reported no effect of naloxone on basal (5,11,14,15,20), stress-, or exercise-induced (1,11,21,22) and TRH-induced (14, 17) levels of PRL. Some studies have found a naloxone-induced inhibition of PRL release (23).…”