Suppression of Luteinizing Hormone Secretion during Food Restriction in Male Rhesus Monkeys (<i>Macaca mulatta</i>): Failure of Naloxone to Restore Normal Pulsatility

Abstract

Short periods of fasting have been shown to cause a significant slowing of pulsatile LH secretion in men and male rhesus monkeys, which appears to result from a slowing of GnRH drive to the reproductive axis. To determine whether an increased activity of endogenous opioid peptides causes this slowing of pulsatile LH secretion, the ability of naloxone administration to reverse the fasting-induced suppression of LH secretion was tested. For this study, 6 adult male rhesus monkeys, with indwelling femoral and jugular venous catheters, were maintained on tether/swivel systems. Naloxone was administered to monkeys as a continuous infusion (0.25 mg/kg/h, with an initial loading dose of approximately 1.0 mg) for 8 h (16.00 to 24.00 h) on a day of normal feeding and again on a day of fasting. The LH response to naloxone was determined by collecting blood samples every 15 min from 12.00 to 24.00 h. LH pulse frequency on a day of normal feeding was 4.0 ± 0.52 pulses/8 h, and naloxone administration on a day of feeding increased LH pulse frequency to 6.8 ± 0.86 pulses/8 h. On a day of fasting, LH pulse frequency was 1.67 ± 0.67 pulses/8 h, and naloxone administration on a day of fasting slightly, but not significantly, increased LH pulse frequency to 2.5 ± 0.51 pulses/8 h. Similar studies were performed with a higher dose of naloxone (0.625 mg/kg/ h, with an initial loading dose of approximately 2.0 mg) and again naloxone administration did not reverse the effects of fasting on pulsatile LH secretion. These results suggest that the slowing of pulsatile LH release that occurs with short periods of food restriction does not result from increased secretion of endogenous opioid peptides.

Neuroendocrine Consequences of Fasting in Adult Male Macaques: Effects of Recombinant Rhesus Macaque Leptin Infusion

“…Consistent with the observations in this study, LH pulse frequency was unchanged in obese men after a 10-day fast [46], in young men following either a 2-day [48]or a 5-day fast [44]or in older men after a 3.5-day fast [45]. Several studies reported a decreased LH pulse frequency after only a 1-day [2, 3, 4, 5, 6]or a 2-day fast [19]in male rhesus macaques and after a 3.5-day fast in young men [45, 49]. However, in the latter study [43]the authors concluded that lower mean LH levels were due largely to a decrease in the amplitude of LH pulses.…”

“…Differences in the physiological role of leptin between species could explain the discrepancies between our results in macaques and those in rodents [14, 43]. However, the reduced mean LH levels and decreased LH pulse frequency in adult [2, 3, 4, 5, 6]and peripubertal [19]rhesus monkeys observed during fasting are relieved in peripubertal male monkeys with recombinant human leptin treatment [19]. Interestingly, testosterone levels in leptin-treated animals were not different from those in fasted controls in that study [19].…”

“…This decrease in frequency occurs without a significant change in body weight [2]and can be rapidly reversed with caloric intake [3]. Changes in insulin [4], endogenous opioids [5]and increased psychological stress [6]have been discarded as causes of fasting-induced decreases in gonadotropin secretion. Chronic elevations in circulating cortisol block gonadotropin secretion by inhibiting the release of GnRH [7].…”

Insulin-Induced Hypoglycemia Decreases Luteinizing Hormone Secretion in the Castrated Male Rat: Involvement of Opiate Peptides

“…Indeed, in ovariectomized female rats, a 120-hour fast induced a reduction in plasma mean LH concentration, but not pulse intervals. This inhibitory effect was reversed by nal oxone injections [10,41], In contrast, in intact male rhe sus monkeys, 1 day of fasting decreased both the mean LF1 pulse frequency and concentration but, in spite of a transient stimulation of LH release immediately after the initiation of the naloxone infusion, this opioid receptor antagonist was unable to restore the normal LH secretory pattern [42], Our results concerning the absence of significant effect of a 0.5-mg/kg/h naloxone infusion on the LH secretory pattern in long-term gonadectomized male rats, are in con trast with the one observed in experiments carried out in intact or in 1-to 2-weck-short-term gonadectomized rats. in which naloxone increased the plasma LH mean concen tration [43][44][45].…”

Fasting-Induced Changes in Pulsatile Luteinizing Hormone (LH) Secretion in Male Rats. The Role of Testosterone and the Hypothalamic Paraventricular Nucleus.

“…Pirke & Spyra [6] first demonstrated that plasma LH concentrations are more reduced by testosterone in fasted males than in unfasted males and concluded that the testosterone feedback system is more sensitive in fasted males than in -Originalccumulating evidence suggests that starvation and malnutrition impair reproductive functions in both sexes in several mammalian species [1][2][3][4][5][6][7]. We have previously shown that pulsatile LH secretion is profoundly suppressed by 48-h fasting in female rats, and that this inhibition is enhanced by estrogen [8,9].…”