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 Zelinski, David Hess, Don P. Wolf, Richard Stouffer

    Research output: Contribution to journalArticle

    Abstract

    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
    Volume79
    Issue number1
    DOIs
    StatePublished - Jul 1994

    Fingerprint

    Luteinizing Hormone
    Gonadotropins
    Population Groups
    Primates
    Progesterone
    Animals
    Granulosa Cells
    Injections
    Oocytes
    Haplorhini
    Luteinization
    Bioassay
    Progesterone Receptors
    Bioactivity
    Luteal Phase
    Corpus Luteum
    Meiosis
    Estradiol
    Menstruation
    Macaca

    ASJC Scopus subject areas

    • Biochemistry
    • Endocrinology, Diabetes and Metabolism

    Cite this

    Initiation of periovulatory events in primate follicles using recombinant and native human luteinizing hormone to mimic the midcycle gonadotropin surge. / Chandrasekher, Yasmin Aladin; Hutchison, James S.; Zelinski, Mary; Hess, David; Wolf, Don P.; Stouffer, Richard.

    In: Journal of Clinical Endocrinology and Metabolism, Vol. 79, No. 1, 07.1994, p. 298-306.

    Research output: Contribution to journalArticle

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    abstract = "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.",
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    AU - Hutchison, James S.

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    AU - Hess, David

    AU - Wolf, Don P.

    AU - Stouffer, Richard

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