INITIATION OF PERIOVULATORY EVENTS IN PRIMATE FOLLICLES USING RECOMBINANT AND NATIVE HUMAN LUTEINIZING-HORMONE TO MIMIC THE MIDCYCLE GONADOTROPIN SURGE

The amplitude and duration of the midcycle LH surge required for perio vulatory changes in the primate follicle are incompletely defined. We reported that short (4- to 14-h) LH surges were insufficient to induce periovulatory events after multiple follicular development in macaque s. In contrast, an 18- to 24-h LH surge induced oocyte maturation plus granulosa cell luteinization, but did not support corpus luteum funct ion. In this study, the periovulatory changes following LH surges of 4 8 h elicited using pituitary (pit) or recombinant (r) human (h) LH wer e compared to those after 24-h LH surge durations or after urinary hCG (u-hCG) treatment. Beginning at menses, rhesus monkeys were treated w ith human gonadotropins for 9 days to stimulate follicular growth. On day 10, animals (n = 3-5/group) received 1) a single injection of u-hC G [79 +/- 3 mu g RP-1 equivalents (equiv), im], 2) two injections of p it-hLH (91 +/- 4 mu g RP-1 equiv, im), 3) one injection of r-hLH (21 /- 1 mu g RP-1 equiv, im), or 4) two injections of r-hLH (21 +/- 1 mu g RP-1 equiv). Oocytes and granulosa cells were obtained via follicle aspiration 27 h after the initial LH or hCG injection. In all groups, serum estradiol rose to similar peak levels by day 10. Circulating LH- like bioactivity was elevated for more than 48 h after u-hCG. Peak ser um LH bioactivites were proportional to the administered LH doses, as determined in the in vitro bioassay. Two injections of either r-hLH or pit-hLH elicited surge levels (>100 ng/mL) of bioactive LH for 36-48 h, whereas one injection sustained surge levels for only 18-24 h. The proportions of oocytes resuming meiosis (68-76%) were similar in all g roups. Immunocytochemical staining for progesterone receptor and in vi tro progesterone production by granulosa cells in all LH-treated group s were comparable to those of cells from the hCG-treated group. Peak l evels of progesterone in the luteal phase were comparable in monkeys t reated with two doses of pit-hLH and r-hLH (18.5 +/- 10.4 vs. 8.1 +/- 1.5 ng/mL) and approached that in u-hCG treated monkeys (39.5 +/- 18.0 ng/mL). However, progesterone levels in animals treated once with r-h LH (3.4 +/- 1.5 ng/mL) were less (P < 0.05) than those in u-hCG-treate d monkeys. The duration of the luteal phase ranged from 8.5 +/- 0.3 da ys in monkeys treated once with r-hLH to 12.4 +/- 0.8 days in u-hCG-tr eated animals. Thus, LH exposure comparable to the interval of the spo ntaneous LH surge (48-50 h) induces periovulatory events similar to th ose elicited by a hCG bolus. Whereas attenuated LH surges of 18-24 h r einitiate oocyte meiosis and promote granulosa cell luteinization, lon ger surges of up to 48 h further promote corpus luteum development and function.