A surge of gonadotropin-releasing hormone accompanies the estradiol-induced gonadotropin surge in the rhesus monkey.

Abstract

In several species, the ovulatory LH surge is preceded by a surge of GnRH. Although a role for estradiol in the initiation of the LH surge is well established in the primate, several observations in the rhesus monkey have questioned whether such an estradiol-induced neurosecretory event takes place. We report on GnRH measurements in cerebrospinal fluid (CSF) samples obtained from the third ventricle of intact and ovariectomized (OVX) conscious rhesus monkeys during control periods and throughout the estradiol-induced positive feedback phase. In the first experiment, we measured control GnRH concentrations in CSF collected at 15-min intervals uninterruptedly for a period of 1-5 days in tethered OVX monkeys (n = 4) in their cages without steroid priming. As had been demonstrated previously with the same method in restrained animals, CSF from the third ventricle contained detectable amounts of GnRH. Spontaneous GnRH secretion was pulsatile; overall mean pulse interval was 67.4 (+/- 2.2 SE) min for a total of 177 GnRH pulses. During 2 periods (8 and 6 h) when simultaneous blood and CSF samples were obtained, 14 out of 15 GnRH pulses were accompanied by an LH pulse. To evaluate the effects of an estrogen challenge on GnRH secretion, estradiol benzoate (E2B; 330 micrograms) was given to 4 intact (5 experiments) and to 2 OVX monkeys. CSF collection was initiated 8-24 h before E2B injection and continued for 72-84 h thereafter. E2B administration resulted in a surge of LH and of GnRH in all but one experiment. The mean time of onset of the GnRH surge was 22.0 (+/- 4.0) h after E2B, whereas that of the LH surge was 24.7 (+/- 3.4) h. In contrast to LH, which declined after a peak at 35.2 +/- 3.9 h, the increase in GnRH secretion persisted throughout most of the observation period. The magnitude of the GnRH response differed in the 2 groups; in the intact animals, mean peak GnRH concentration increased 8.9-fold but only 3.8-fold in the OVX monkeys. A similar GnRH surge was observed in 1 OVX monkey, receiving an iv infusion of E2, which produced more physiological concentrations of E2. In this animal, an initial suppression of GnRH concentration in the 24-48 h period after E2 (GnRH control, 14.6 +/- 1.9; post-E2, 4.0 +/- 0.5 pg/ml) preceded the initiation of the GnRH surge which occurred at 54 h after E2.(ABSTRACT TRUNCATED AT 400 WORDS)

Decreased release of gonadotropin-releasing hormone during the preovulatory midcycle luteinizing hormone surge in normal women.

“…This finding is supported by earlier observations in rhesus monkeys that GnRH antisera do not block sex steroid-induced gonadotropin surges (29) and that a gonadotropin surge can be generated in response to estrogen in the absence of GnRH for up to 24 hr (30). However, recent studies in rhesus monkeys indicate that GnRH levels are increased in both spontaneous and steroid-induced gonadotropin surges (8,9). Our findings in normal women are, therefore, not in agreement with direct measurement of GnRH in monkeys, sheep, and rats that have demonstrated variable increases in the amount of GnRH during gonadotropin surges (4-9).…”

“…GnRH levels also appear to increase at the time of the proestrus surge in rats (7) and rhesus monkeys (8,9). These direct techniques of accessing information regarding the hypothalamic component of the preovulatory surge are clearly not feasible in the human and measurements of GnRH in the peripheral circulation do not accurately reflect hypothalamic GnRH secretion ifat all (10).…”

Diurnal and estradiol-dependent changes in gonadotropin-releasing hormone neuron firing activity

“…Studies of rats and sheep have indicated that a GnRH surge accompanies and is required for the LH surge (7)(8)(9)42), and more recent studies in rhesus monkeys have indicated that a GnRH surge is present and required in this species as well (10,43). In rodents, the amplitude of the GnRH surge has been reported to be too small to trigger a LH surge without an accompanying increase in pituitary responsiveness to GnRH (44,45).…”

New insights into the classical and non-classical actions of estrogen: Evidence from estrogen receptor knock-out and knock-in mice

“…For example, prolonged estrogen exposure is required for positive feedback and maximum pituitary responsiveness to GnRH in the rat (Legan et al, 1975), mouse (Bronson, 1981), monkey (Xia et al, 1992), and ewe (Evans et al, 1997), suggesting that slower, genotropic actions are involved in this process. Interestingly, GnRH surges can occur even after estrogen withdrawal, suggesting that the neuronal network supporting the surge process is sufficiently activated by previous E 2 exposure and does not require short-term E 2 action (Evans et al, 1997).…”