Intraluteal infusion of a prostaglandin synthesis inhibitor, sodium meclofenamate, causes premature luteolysis in rhesus monkeys

Eva L. Sargent, William L. Baughman, Miles J. Novy, Richard L. Stouffer

    Research output: Contribution to journalArticlepeer-review

    32 Scopus citations

    Abstract

    The physiological significance of locally produced prostaglandins (PGs) in the regulation of the functional lifespan of the primate corpus luteum is unknown. In the current study, the PG synthesis inhibitor sodium meclofenamate was administered to adult female rhesus monkeys beginning in the midluteal phase of the menstrual cycle. Meclofenamate was infused continuously for 7 days into the corpus luteum (100 µg/ h, n = 6) or the jugular vein (100 µg/h, n = 3; 1000 µg/h, n = 3) via osmotic minipump. As controls, PBS was infused into the corpus luteum (n = 7) or jugular vein (n = 5). In some of the monkeys receiving intraluteal infusions, chronic aortic and utero-ovarian venous catheters were implanted, and blood samples were collected on alternate days for the measurement of PGE and PGF by RIA. Saphenous venous blood was collected daily, and progesterone and cortisol levels were determined by RIA. LH levels were determined by the mouse Leydig cell bioassay. Progesterone levels over 5 days preceding treatment were not different among groups. A decline in progesterone levels on day 1 after surgery was observed in all treatment groups and was accompanied by a 1-day elevation in cortisol levels. Thereafter, five of seven monkeys who received intraluteal infusions of PBS displayed normal progesterone patterns during treatment and normal luteal phase lengths of 15.4 ± 1.2 days (mean ± SEM). In six monkeys that received intraluteal infusions of meclofenamate, progesterone levels typically fell to less than 1 ng/ml within 72 h after initiation of infusion; progesterone levels during 7 days of intraluteal infusion were significantly lower (P <0.01) in meclofenamate- vs. PBS-treated monkeys. Meclofenamate infusion into the corpus luteum significantly shortened (P < 0.01) the luteal phase to 10.5 ± 1.0 days. In contrast, progesterone levels during 7 days of meclofenamate infusion into the jugular vein did not differ from those in PBS-treated monkeys, and the length of the luteal phase was unaltered. LH levels, measured daily, did not differ among groups either before or during treatment. Although ah venous/arterial gradient in PGE was detected at the time of surgery, we were unable to detect a significant gradient across the ovary in PGE or PGF at any time after surgery in monkeys treated with either PBS or meclofenamate. The present data suggest an obligatory luteotropic role for locally produced metabolites of arachidonic acid, but a physiological role for either PGE or PGF in regulating the primate corpus luteum remains equivocal.

    Original languageEnglish (US)
    Pages (from-to)2261-2269
    Number of pages9
    JournalEndocrinology
    Volume123
    Issue number5
    DOIs
    StatePublished - Nov 1988

    ASJC Scopus subject areas

    • Endocrinology

    Fingerprint Dive into the research topics of 'Intraluteal infusion of a prostaglandin synthesis inhibitor, sodium meclofenamate, causes premature luteolysis in rhesus monkeys'. Together they form a unique fingerprint.

    Cite this