Synergistic effects of antiprogestins and iNOS or aromatase inhibitors on establishment and maintenance of pregnancy

Leili Shi, Shao Qing Shi, Randall L. Given, Helena Von Hertzen, Robert E. Garfield

    Research output: Contribution to journalArticle

    18 Citations (Scopus)

    Abstract

    Progesterone is known to be involved in many steps in female reproduction including control of implantation and uterine-cervical function during pregnancy. Our studies in rats and guinea pigs indicate that progesterone inhibits uterine contractility and cervical softening during pregnancy. Progesterone levels or actions decline near the end of pregnancy leading to the onset of labor. Treatment with progestin agonists prolongs pregnancy and inhibits cervical softening, whereas treatment with antiprogestins (mifepristone or onapristone) stimulates uterine contractility, cervical softening and premature delivery. Thus the effect of progesterone receptor modulators in the uterus and cervix depend up on the degree of intrinsic agonistic/antagonistic activities. Our recent studies show that progesterone interacts with nitric oxide (NO) to maintain pregnancy and that administration of progesterone antagonists with NO synthase inhibitors act synergistically to stimulate labor. In addition our studies show that combinations of progesterone antagonists with aromatase inhibitors act synergistically to induce labor. Similarly antiprogestins interact with NO synthase or aromatase inhibitors to block implantation through action on the endometrium. These studies suggest new applications for combined therapies of progestin receptor modulators with aromatase inhibitors or agents that modify NO production for contraception, stimulation of labor, estrogen-dependent diseases and improved outcomes in pregnancy.

    Original languageEnglish (US)
    Pages (from-to)1077-1084
    Number of pages8
    JournalSteroids
    Volume68
    Issue number10-13
    DOIs
    StatePublished - Nov 2003

    Fingerprint

    Pregnancy Maintenance
    Aromatase Inhibitors
    Progesterone
    Pregnancy
    Personnel
    Progesterone Receptors
    Nitric Oxide Synthase
    Modulators
    Nitric Oxide
    Labor Onset
    Mifepristone
    Progestins
    Pregnancy Outcome
    Endometrium
    Contraception
    Cervix Uteri
    Reproduction
    Rats
    Estrogens
    Guinea Pigs

    Keywords

    • Antiprogestin
    • Aromatase inhibitor
    • Implantation
    • iNOS
    • Pregnancy
    • Preterm birth
    • Progesterone

    ASJC Scopus subject areas

    • Biochemistry
    • Endocrinology
    • Molecular Biology

    Cite this

    Synergistic effects of antiprogestins and iNOS or aromatase inhibitors on establishment and maintenance of pregnancy. / Shi, Leili; Shi, Shao Qing; Given, Randall L.; Von Hertzen, Helena; Garfield, Robert E.

    In: Steroids, Vol. 68, No. 10-13, 11.2003, p. 1077-1084.

    Research output: Contribution to journalArticle

    Shi, Leili ; Shi, Shao Qing ; Given, Randall L. ; Von Hertzen, Helena ; Garfield, Robert E. / Synergistic effects of antiprogestins and iNOS or aromatase inhibitors on establishment and maintenance of pregnancy. In: Steroids. 2003 ; Vol. 68, No. 10-13. pp. 1077-1084.
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