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

Abstract

The activity of the GnRH pulse generator in the rhesus monkey is associated with abrupt increases in multiunit electrical activity (MUA) volleys recorded from the mediobasal hypothalamus that precede each pulse of LH in the peripheral circulation. In long-term ovariectomized animals the duration of these MUA volleys is 10–25 min and consists of a brief initial ‘overshoot’ followed by a plateau phase that ends in a rapid decline to baseline activity. In intact monkeys, however, the MUA volley lasts only 1–3 min, a duration equivalent to the overshoot in ovariectomized animals. In addition, the maximal frequency of neuronal activity during each MUA volley is reduced in normal animals when compared to castrates. As shown in earlier studies, estradiol given to ovariectomized monkeys causes a reduction in the duration of MUA volleys to that characteristic of intact animals within 3–5 h. In contrast to this acute effect of estradiol, the increase in MUA volley duration following ovariectomy is a gradual phenomenon, 4–6 weeks being required to achieve the MUA volley duration observed in long-term ovariectomized monkeys. A similar slow time course was observed for the increase in maximal neuronal frequency during each MUA volley. This protracted effect of ovariectomy on MUA volley duration and firing rate may be the consequence of hypothalamic remodelling but this consideration must be tempered by the observation that estradiol reverses these phenomena within hours.

Single unit components of the hypothalamic multiunit electrical activity associated with the central signal generator that directs the pulsatile secretion of gonadotropic hormones.

“…Sixteen of the 26 units identified in ovariectomized and 8 ofthe 14 units found in intact rhesus monkeys had bursts with onsets and terminations invariably coincident with those of the MUA volleys, indicating that the longer duration of the MUA volleys characteristic of the gonadectomized animals [10-25 min, in contrast to the 1-to 3-min duration that can be found in intact monkeys (20)] was due not to the sequential activation of different units but to the longer bursts of the individual cells contributing to the MUA volleys (Fig. 3, units 1L, 2L, and 4R; Fig.…”

Premature elevation in serum insulin-like growth factor-I advances first ovulation in rhesus monkeys

“…However, those neuroendocrine mechanisms themselves are still undefined. In adult animals, gonadal steroids inhibit LH secretion by decreasing the activity of neurons in the mediobasal hypothalamus (O'Bryne et al 1993), resulting in a decrease in LHRH biosynthesis (Toranzo et al 1989) and release (Karsch et al 1987). Since LHRH neurons do not contain estrogen receptors, these inhibitory effects of estradiol on LHRH biosynthesis and release are complex and probably involve an interneuronal pathway (Herbison et al 1995, Sullivan et al 1995, possibly the activation of the inhibitory neurotransmitter -aminobutyric acid (GABA) in discrete hypothalamic neurons (Herbison et al 1991, McRee & Meyer 1993.…”

Estradiol and the inhibition of hypothalamic gonadotropin-releasing hormone pulse generator activity in the rhesus monkey.

“…Moreover, the gradual recovery of the amplitude and duration of the single-unit bursts and of the resultant MUA volleys continued and was still not complete 7-20 days after estradiol had returned to preinjection levels. This finding, which is very similar to that observed after ovariectomy (31), is inconsistent with an opioid mediation of the steroid-induced inhibition and suggests that the protracted effects of exogenous or endogenous estrogen withdrawal may reflect a structural remodeling in the hypothalamus (32)(33)(34) as discussed in detail elsewhere (31).…”