Initiation of periovulatory events in primate follicles using recombinant and native human luteinizing hormone to mimic the midcycle gonadotropin surge

Yasmin Aladin Chandrasekher, James S. Hutchison, Mary B. Zelinski-Wooten, David L. Hess, Don P. Wolf, Richard L. Stouffer

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64 Scopus citations


The amplitude and duration of the midcycle LH surge required for periovulatory 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 macaques. In contrast, an 18- to 24-h LH surge induced oocyte maturation plus granulosa cell luteinization, but did not support corpus luteum function. In this study, the periovulatory changes following LH surges of 48 h elicited using pituitary (pit) or recombinant (r) human (h) LH were compared to those after 24-h LH surge durations or after urinary hCG (u-hCG) treatment. Beginning at menses, rhesus monkeys were treated with human gonadotropins for 9 days to stimulate follicular growth. On day 10, animals (n = 3-5/group) received 1) a single injection of u-hCG [79 ± 3 μg RP-1 equivalents (equiv), im], 2) two injections of pit-hLH (91 ± 4 μg RP-1 equiv, im), 3) one injection of r- hLH (21 ± 1 μg RP-1 equiv, im), or 4) two injections of r-hLH (21 ± 1 μg 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 serum 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 groups. Immunocytochemical staining for progesterone receptor and in vitro progesterone production by granulosa cells in all LH-treated groups were comparable to those of cells from the hCG- treated group. Peak levels of progesterone in the luteal phase were comparable in monkeys treated 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- hLH (3.4 ± 1.5 ng/mL) were less (P < 0.05) than those in u-hCG-treated monkeys. The duration of the luteal phase ranged from 8.5 ± 0.3 days in monkeys treated once with r-hLH to 12.4 ± 0.8 days in u-hCG-treated animals. Thus, LH exposure comparable to the interval of the spontaneous LH surge (48- 50 h) induces periovulatory events similar to those elicited by a hCG bolus. Whereas attenuated LH surges of 18-24 h reinitiate oocyte meiosis and promote granulosa cell luteinization, longer surges of up to 48 h further promote corpus luteum development and function.

Original languageEnglish (US)
Pages (from-to)298-306
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Issue number1
StatePublished - Jul 1994

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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