Circhoral Oscillations of Plasma LH Levels in the Ovariectomized Rhesus Monkey¹,²

Abstract

Blood samples were withdrawn at 10-, 20-or 30-min intervals for 6-12 hr from 13 ovariectomized and 7 intact female rhesus monkeys bearing indwelling cardiac catheters and restrained in primate chairs. Plasma LH and GH concentrations were determined by radioimmunoassay. Twenty-four experiments in ovariectomized animals revealed a striking rhythmic pattern in plasma LH levels having a period of approximately 1 hr, which was asynchronous with variations in plasma GH concentrations when these occurred. The LH oscillations, which had an excursion of 40-92 % of the mean hormone concentration, occurred with a mean period of 75 min and a mode of 60 min. In a typical rhythmic sequence, LH levels increased from nadir to peak during one 10-min sampling interval and decayed exponentially for the next 60 min. The t } calculated from 19 such decay curves based on 10-min sampling intervals was 72 min, which is similar to the estimated tj of exogenous LH in intact females. Moreover, there was a significant positive correlation between the duration of the decay and the magnitude of the next peak. Such oscillations did not occur in intact females. It is suggested that these circhoral (about an hr) oscillations in plasma LH concentrations, occasioned by ovariectomy, represent pulsatile discharges of LH from the pituitary and probably account for the greater part of the elevated LH plasma levels seen in ovariectomized animals. (Endocrinology 87: 850, 1970) I N THE course of experiments performed in bilaterally ovariectomized rhesus monkeys, sampled at relatively frequent intervals, circulating levels of LH were observed to be markedly unstable (1). On detailed examination, sharp oscillations in plasma LH concentrations with a periodicity of approximately one hour were revealed. The following report describes this unexpected phenomenon. Materials and MethodsThirteen adult female rhesus monkeys (Macaco mulatto), weighing 4.6-6.2 kg, were bilaterally ovariectomized under pentobarbital anesthesia and utilized 2 weeks to 7 months after ovariectomy. Seven intact females in the same weight range were also studied.

Indirect assessment of pulsatile gonadotropin-releasing hormone release in agonadal prepubertal rhesus monkeys (Macaca mulatta)

“…In the adult ovariectomized monkey, the circhoral release of GnRH results in mean levels of circulating LH ranging in general from 100 to 200 ng/ml (Dierschke et al 1970), concentrations which were frequently observed in the present study in response to the nocturnal release of pulsatile GnRH from the hypothalamus of the 15-to 20-month-old female. While the relationship between frequency and amplitude modulation of a pulsatile pattern of GnRH stimulation, on the one hand, and its strength as a drive to the gonadotroph, on the other, is complex, similar levels of mean LH are intuitively equated to comparable GnRH drives.…”

“…In such studies, inter-GnRH-pulse intervals of approximately 1 h have been described for juvenile ovariectomized monkeys . In adult ovariectomized monkeys, direct and indirect assessment of GnRH pulse frequency has yielded comparable estimates of this parameter, namely approximately 1 pulse/h (Dierschke et al 1970, Wilson et al 1984, Gearing & Terasawa 1991. Since the present indirect analysis of GnRH pulse frequency in the prepubertal animal employed a pituitary with a responsiveness similar to that in the adult, the lack of congruency between the results obtained by the two methods in the prepubertal state must therefore be related to the smaller GnRH signal at this stage of development.…”

Studying sex and gender differences in pain and analgesia: A consensus report

“…First, surgery can affect pain thresholds [93,173] and sensitivity to analgesics. Second, gonadectomy disrupts the normal feedback loop that sex steroids exert on the anterior pituitary and hypothalamus, leaving both males and females in a prolonged state of elevated (e.g., gonadotropin-releasing hormone (GnRH), leuteinizing hormone) or depressed (e.g., prolactin) circulating hormones [1,53,95,220]. The likelihood of unintended consequences due to altered hypothalamic/pituitary hormone secretion can be addressed by administering low (maintenance) doses of estradiol or testosterone rather than using gonadectomized animals with no hormone replacement.…”

Hypothalamo-pituitary-gonadal Axis

“…Had it not been for Harris' untimely death at an age of 58 he surely would have shared this most prestigious of awards for laying the conceptual underpinnings for the work of Schally and Guilleman! In 1969, two years before Schally and Guilleman reported the isolation of GnRH, Knobil's laboratory studying the ovariectomized rhesus monkey had found that LH was secreted in a pulsatile or episodic manner with a frequency in the agonadal condition of approximately 1 pulse per hour: they proposed that this pulsatile mode of LH secretion may be due to intermittent signals from the central nervous system that are relayed to the pituitary by an LH releasing factor (Dierschke, et al 1970;Knobil 1992). Knobil's laboratory went on to demonstrate in 1978 that intermittent GnRH stimulation of the pituitary was essential for sustained secretion of both LH and FSH (Belchetz, et al 1978) (Figure 2).…”