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Hormonal Regulation of Interstitial Collagenase in the Uterine Cervix of the Pregnant Guinea Pig^*

Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, and Departments of Biochemistry and Surgery, McGill University and Joint Diseases Laboratory, Shriners Hospital for Crippled Children Montreal, Quebec, Canada

Address all correspondence and requests for reprints to: Dr. Mohammad R. Rajabi, Royal Victoria Hospital, Women's Pavilion, Room F4- 32, 687 Pine Avenue West, Montreal, Quebec, Canada H3A 1A1.

Abstract

The uterine cervix is a hormonally responsive organ whose function is tightly regulated during pregnancy. Interstitial collagenase is believed to play a key role in the mechanism of cervical dilatation. This study examines the hormonal regulation of procollagenase gene expression in primary monolayer cell cultures derived from cervices of 50-day pregnant guinea pigs. Procollagenase production was constitutive in these cells. Activity was stimulated up to 2-fold by interleukin 1β,17β- estradiol, and estrone. The effect of estradiol was completely inhibited by indomethacin and the estrogen antagonist, tamoxifen. The endogenous and the stimulated procollagenase were completely blocked by cycloheximide and by actinomycin D, indicating the need for protein and messenger RNA (mRNA) synthesis, respectively. Progesterone and 17-OH progesterone also stimulated procollagenase production at physiological concentrations (10^-8 M). The stimulatory effect of progesterone was blocked by the antiprogesterone RU38486. Procollagenase mRNA was stimulated by interleukin 1β (5 U/ml) and by 17β- estradiol (10^-10–10^-8 M) and progesterone (10^-8 M). But progesterone at 10^-4 M completely blocked the stimulatory effect of 17β-estradiol on procollagenase mRNA. Increased availability of prostaglandins by mobilization of arachidonic acid by phospholipase A₂ or by the addition of prostaglandin F₂ and prostaglandin E₂ resulted in a 2-fold increase in procollagenase activity in culture media. These studies demonstrate that procollagenase gene expression is hormonally controlled in the cervix of pregnant guinea pig. (Endocrinology 128: 863–871, 1990)

Footnotes

^* This work was supported by the Medical Research Council of Canada and the Shriners of North America.

Received July 5, 1990.

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