Naloxone Stimulation of Luteinizing Hormone Secretion in the Female Monkey: Influence of Endocrine and Experimental Conditions^*

Abstract

It is known that opiate administration results in the inhibition of LH release. In this paper, we examine the role of endogenous opiates in the regulation of gonadotropin secretion during the menstrual cycle of the monkey. The objectives of these experiments were to determine the experimental and endocrine conditions that are conducive to increased gonadotropin secretion in response to endogenous opiate antagonism. In Exp 1, naloxone was administered during the luteal phase to three groups of monkeys under three different experimental conditions. When naloxone (2 mg, iv) was injected into conscious unrestrained or sedated animals, LH secretion increased 2- to 3-fold. In contrast, the same dose of naloxone failed to stimulate LH secretion in monkeys restrained in primate chairs. In Exp 2, the gonadotropin response to acute naloxone administration on each day of the menstrual cycle was determined. A significant increase in the serum LH concentration (greater than or equal to 20% within 40 min of injection) was observed after naloxone administration in 60% of the trials conducted during the luteal phase. Significant increases occurred in only 13% of the saline-treated control trials during this stage of the menstrual cycle. Mean LH levels increased from 14.4 +/- 1.3 to 31.2 +/- 4.3 ng/ml after naloxone injection. In contrast, naloxone had no effect on LH secretion during the follicular phase. Although small LH increments were noted after naloxone injection in 40 +/- 8% of the trials, neither the frequency nor the amplitude of these increases was different from that in follicular phase controls. We conclude from these results that the ability of naloxone to stimulate LH secretion is limited to the luteal phase. Previous findings from our laboratory indicate that hypothalamic beta-endorphin activity, as reflected by its concentration in hypophyseal portal blood, is increased by ovarian steroids and that its greatest activity occurs during the luteal phase. Since the response of LH to naloxone administration was limited to the luteal phase, we believe that these results support the conclusion that hypothalamic beta-endorphin is a physiological modulator of LH secretion in the monkey.

Naloxone evokes large-amplitude GnRH pulses in luteal-phase ewes

“…This was expected since FSH does not appear to be acutely regulated by GnRH in the sheep (Clarke & Cummins, 1985b). Other work in the rat (Sirinanthsinghji & Martini, 1985;Piva et al, 1985), monkey (Van Vugt et al, 1983) and human (Foresta et ai, 1983;Snowden et al, 1984) has also indicated that FSH is unresponsive to naloxone treatment, perhaps for similar reasons. However, Ropert et al (1981) have shown that FSH does respond to an infusion of naloxone in women.…”

“…Brooks et al (1986b) also noted that the ability of naloxone to increase LH secretion in Suffolk-cross ewes varied, and further showed that there was no dose-response relationship between 25 and 100 mg/h. Similarly, Van Vugt et al (1983) demonstrated that only 60% of lutealphase monkeys had an LH response to naloxone. Finally, chronic treatment of rams with naloxone led to a loss of responsiveness after 3 days (Ebling & Lincoln, 1985).…”

“…In contrast, naloxone increased LH pulse frequency in the luteal but not the follicular phase of women (Moult et ai, 1981) and monkeys (Van Vugt et al, 1983). It is possible that sheep are different from monkeys and humans in their ability to respond to naloxone during the follicular phase of the oestrous/menstrual cycle.…”

Environment, human reproduction, menopause, and andropause.

“…Mild stress (chair restraint) in nonhuman primates arrests the GnRH pulse generator (8), an effect mediated by the corticotropin-releasing factor (CRF) (9,10). CRF infusion in humans causes an inhibition of pulsatile LH release (11).…”

The potency of mu-opioid hyperpolarization of hypothalamic arcuate neurons is rapidly attenuated by 17 beta-estradiol

“…When estrogen levels are high, injection of the p-endorphin antagonist naloxone increases serum LH levels and can even advance the LH surge in women by an average of 2 d (Rossmanith et al, 1988). In contrast, naloxone has very little effect on LH release when E, levels are low (Van Vugt et al, 1983). Ovariectomy in rats results in an increase in basal LH levels that are reduced by injection of estradiol (Legan et al, 1973).…”