Preovulatory gonadotropin-releasing hormone surge in ovarian-intact rhesus macaques

The occurrence and profile of the preovulatory hypothalamic GnRH surge in relation to plasma profiles of LH and ovarian steroids, i.e. 17-estradiol (E₂) and progesterone (P4), were examined in ovarian intact, freely moving rhesus macaques. Nine monkeys with active ovarian cycles were each fitted with a jugular venous catheter and two push-pull cannulae directed to separate sites within the median eminence (ME). Each female was connected continuously to a tether/ swivel device through which daily blood samples or frequent blood samples and ME perfusates (simultaneously at 10-to 20-min intervals for 18-24 h) were obtained without disturbing the animals. An increment in the plasma E₂ level (>150 pg/ml) during the follicular phase (FP) was selected as the preovulatory ovarian signal and served as the index for initiating the ME push-pull perfusion (PPP). Daily increased P₄ concentrations of more than 1 ng P₄/ml plasma for several consecutive days were consistent with the assumption of ovulation and subsequent formation of a corpus luteum after PPP. A total of 18 PPP trials were completed; each in a fresh ME site. Five of these PPPs were performed during the mid-and late FP (3 were between 6-8 days before and 2 were 4 days before the E₂ peak). The remaining 13 PPPs, each of 18-to 24-h duration, were performed between 24 h before and 48 h after the highest daily plasma E₂ level, i.e. time zero. Of these 13 PPPs, 2 started within 12 h before (-12 to 0 h), 8 began within 12 h after (012 h), and 3 started between 12-24 h after this peak E₂ value. During the FP, mean levels of GnRH and LH were less than 2 pg/ml and 20 ng/ml, respectively. During the periovulatory interval (—24 to 48 h around time zero), the release of hypothalamic GnRH (expressed in picograms per ml) increased to 6.63 ± 2.35 between —12 to 0 h (n = 2), peaked at 20.70 ± 6.09 between 0-12 h (n = 10), declined to 3.25 ± 1.39 between 12-24 h (n = 11), and further declined to 0.89 ± 0.18 between 24-36 h (n = 3). The mean GnRH value from 0-12 h was higher (P < 0.05) than other means (including those during the FP), except for the value between -12 to 0 h. Changes in mean plasma LH values during the same periods paralleled those in GnRH. The highest LH mean occurred between 0-12 h (269.49 ± 72.08 ng/ml), and this value exceeded all other means (P < 0.05). Collectively, these data depict an unambiguous rise and fall in ME GnRH release paralleled in time by a corresponding rise and fall in plasma LH levels and a subsequent increase in daily P4 values of more than 1 ng/ml. These observations support the concept that in naturally cycling primates, ovulation is triggered by a cascade of neuroendocrine events; these culminate in a dramatic release of hypothalamic GnRH, which thereby stimulates gonadotropes to release LH, i.e. the preovulatory surge.