Endogenous Opioid Peptides Modulate the Effect of Corticotropin-Releasing Factor on Gonadotropin Release in the Primate*

Abstract

Stress can induce endocrine abnormalities and menstrual dysfunction in the primate. Here, we examine the effects that CRF, the principal neurohormone in control of the hypothalamic-pituitary-adrenal axis, exerts on pulsatile gonadotropin secretion and the role that the endogenous opioid peptides may play in this phenomenon. Ovariectomized rhesus monkeys were given a 5-h continuous iv infusion of physiological saline (2 ml/h), human CRF (100 .mu.g/2 ml .cntdot. h), or hCRF plus the opiate receptor antagonist naloxone (2 mg/2ml/h; 5 mg in two experiments; n = 7 experiments/group). LH and FSH concentrations were measured at 15-min intervals for a 3-h preinfusion baseline control, during the 5-h infusion, and during a 2-h postinfusion observation period, while cortisol concentrations were measured at frequent intervals during the entire experiment. CRF infusion produced a progressive and significant decrease in both LH and FSH. Mean areas (.+-.SE) under the LH and FSH curves during the 5-h CRF infusion, expressed as a percentage of preinfusion baseline were 59.9 .+-. 4.6% and 83.0 .+-. 3.1% (.+-.SE), respectively (P < 0.001 and P < 0.01 vs. saline controls). Large amplitude LH pulses were abolished during the CRF infusion. However, after cessation of CRF infusion, there was a rapid resumption of LH pulsatile release in four of the seven experiments. Addition of naloxone to CRF prevented the CRF- mediated suppression of LH and FSH release. Mean areas for LH and FSH during the 5-h combined infusion were 100.3 .+-. 6.6% and 99.6 .+-. 4.3% of the preinfusion baseline, respectively (P < 0.001 and P < 0.05 vs. CRH alone; NS vs. saline), and pulsatile LH secretion was maintained. Regardless of whether naloxone was administered, CRF increased cortisol levels significantly. Mean cortisol levels at the end of the CRF and CRF plus naloxone infusions were 48.2 .+-. 10.4 and 52.9 .+-. 7.4 .mu.g/dl (.+-.SE), respectively, compared to 21.0 .+-. 3.0 with saline (P < 0.05). These results demonstrate that in the ovariectomized rhesus monkey, CRF suppresses the secretion of both LH and FSH, and this effect can be sustained. They also indicate that the CRF inhibitory action on gonadotropin is primarily mediated by endogenous opioid peptides, independent of glucocorticoid levels.