In vivo gonadotropin-releasing hormone release and serum luteinizing hormone measurements in ovariectomized, estrogen-treated rhesus macaques

The push-pull perfusion technique was used to measure GnRH release in unanesthetized female rhesus macaques (Macaco mulatto) and to examine the dynamic relationship between GnRH release and LH levels during the estrogeninduced LH surge. Each ovariectomized macaque was anesthetized and stereotaxically fitted with a push-pull cannula directed into the median eminence (ME). After at least 1 week of recovery, each animal received an estradiol benzoate (E₂B) injection (42 μg/kg BW) or an oil (OIL) injection and underwent pushpull perfusion of the ME and blood sampling for at least 5 h between 28 and 56 h postinjection. Continuous 10-min pushpull perfusates were collected and prepared for GnRH RIA. Peripheral venous blood samples were obtained either hourly or every 10 min, and serum LH levels were determined by Leydig cell bioassay. GnRH release was detectable and pulsatile in areas in or adjacent to the ME or arcuate nucleus. In eight OIL monkeys, GnRH pulses were regular (∼one pulse every 60 min) and of low amplitude (14.7 ± 12.0 pg), with a mean GnRH release rate of 4.0 ± 1.7 pg/10 min. In five E₂B-treated monkeys, GnRH release during the rising phase of the LH surge occurred as an apparent burst of high amplitude GnRH pulses. The mean GnRH release rate (37.5 ± 17.9 pg/10 min) and mean GnRH pulse amplitude (170.0 ± 90.0 pg) during the 5 h before the peak LH level in E₂B-treated monkeys were greater than OIL values (P < 0.025, mean release; P < 0.05, mean amplitude). Within individual E₂B-treated monkeys, hourly mean GnRH release rates were significantly correlated with LH levels during the ascending limb of the LH surge (r = 0.75 ± 0.11; P < 0.025). We have concluded that an increase in GnRH neurosecretion occurs in E₂B-treated monkeys and that it is associated with generation of the LH surge. On the basis of our observations, we hypothesize that the primate hypothalamus, through changes in GnRH secretion, actively participates in the E₂B-induced LH surge.