Effects of Naloxone on Estrogen-Induced Changes in Hypothalamic Gonadotropin-Releasing Hormone Pulse Generator Activity in the Rhesus Monkey

Abstract

In the ovariectomized rhesus monkey, estradiol (E₂) markedly reduces the frequency of the GnRH pulse generator as monitored by LH pulse frequency and the concurrent changes in hypothalamic electrical activity, an action mimicked by morphine. In addition, the duration of the increments in multiunit electrical activity (MUA volleys) that precede each LH pulse is decreased by estrogen administration, an action also shared by morphine. The role of endogenous opioids in these actions of E₂ was investigated in 8 ovariectomized animals restrained in primate chairs. They were fitted with indwelling cardiac catheters and with bilateral arrays of recording electrodes chronically implanted in the mediobasal hypothalamus. Physiological serum E₂ levels achieved by subcutaneous implantation of E₂-containing Silastic capsules increased MUA volley interval from 50.8 ± (SEM) 1.6 min in the control period to 81.1 ± 6.2 min following E₂. Mean MUA volley duration decreased from 21.9 ± 1.0 to 13.0 ± 0.7 min. The placement of empty Silastic capsules had no effect on MUA volley duration or interval. Naloxone administration (2.5 mg bolus followed by a 1 mg/h infusion lasting 4-8 h) completely (n = 4) or partially (n = 2) blocked the effects of E₂ on MUA volley interval in 6 of the 8 monkeys, and was without effect in the remainder. In contrast, however, naloxone had little or no effect on the action of E₂ on MUA volley duration, (13.0 ± 0.7 vs. 14.0 ± 0.9 min). These findings suggest that the inhibitory action of E₂ on GnRH pulse generator frequency, like that of all other gonadal steroids studied to date, may be mediated by endogenous opioids. The equally striking inhibitory effect of E₂ on pulse generator MUA volley duration, however, an effect that can also be replicated by morphine administration, seems to be principally effected by other mechanisms.

Changes in the Gonadotropin- Releasing Hormone Pulse Generator Activity during the Estrous Cycle in the Goat

“…On the other hand, the present results indi cated that the duration of MUA volley, in other words each activation of GnRH pulse generator, changed ac cording to the stage of estrous cycle. In the rhesus monkey, the duration of the MUA volley gradually prolonged after ovariectomy [23] and was shortened by estradiol injection up to physiological levels [24,25], Similarly, in ovariecto mized goat, constant estradiol infusion induced a reduc tion in MUA volley duration [12], In the present study, the volley duration was generally short in the follicular phase and was gradually shortened along with the preovu latory rise in plasma estradiol levels during the follicular phase. These results suggest that estradiol may be a factor responsible for suppressing the duration of the MUA vol ley.…”

Phytoestrogens and Gonadotropin-Releasing Hormone Pulse Generator Activity and Pituitary Luteinizing Hormone Release in the Rat*

“…In addition to the pituitary, the hypothalamus is a site of negative feedback regulation by estradiol, as indicated by a reduction in GnRH pulse generator frequency (22,31). The present study provides the first evidence that the phytoestrogen, coumestrol, has a similar central action.…”

Ovarian Control of Gonadotropin Hormone-Releasing Hormone Pulse Generator Activity in the Rhesus Monkey: Duration of the Associated Hypothalamic Signal

“…In the ovariectomized monkey, morphine results in a decrease in both MUA volley duration and frequency [20,21], as does estrogen [3]. While the effect of estrogen on pulse generator fre quency' is blocked by naloxone, the action of the steroid on MUA volley duration is insensitive to opioidergic blockade [22], It is unlikely, therefore, that the gradual increase in MUA volley duration following ovariectomy results from a change in opioidergic tone although nonestrogenic mechanisms may well be involved. Castration is associated with other morphological al terations in the mediobasal hypothalamus.…”