Studies were designed to investigate the biochemical mechanism and hormonal regulation of dilatation of the uterine cervix at parturition. The suitability of the guinea pig animal model was established by demonstrating collagenolysis in the uterine cervix similar to the changes reported in women by light and electron microscopy. By 50 days gestation, there was a 50% decrease in collagen content in the cervix. At parturition (68 $ pm$ 2 days) there was a 6-fold increase in procollagenase, a 26-fold increase in the tissue inhibitor of metalloproteinase (TIMP) and a 2-fold increase in net collagenase activity in cervical extracts. Cervices in organ culture obtained at birth produced 2.9 times more procollagenase, 1.6 times more TIMP and a 10-fold increase in net collagenase activity when compared to nonpregnant or 25 days pregnant animals. Estradiol stimulated the production of procollagenase, TIMP and net collagenase activity in cervical organ cultures. Using primary monolayer cervical cell cultures derived from 50 day pregnant guinea pigs, procollagenase enzyme and its mRNA were stimulated up to 2-fold by recombinant human interleukin 1$ beta$ (IL-1$ beta$), estrogens and progesterone. Procollagenase production was completely abolished by cycloheximide and by actinomycin D indicating the need for translation and transcription respectively. The mechanism of signal transduction of procollagenase was also investigated. A rabbit polyclonal antiserum (R4718) that specifically reacts with epitopes on denatured and degraded $ alpha$2 chain of guinea pig type I collagen was used to demonstrate degradation of type I collagen in the extracellular matrix of the dilated cervix at parturition. Physiological concentrations of 17$ beta$-estradiol stimulated degradation of type I collagen in the nonpregnant cervix in organ culture. This effect was completely blocked by progesterone (100 $ mu$M). These studies indicate that cervical dilatation at parturition involves estrogen-indu
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.74615 |
| Date | January 1990 |
| Creators | Rajabi, Mohammad R. (Mohammad Refai) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Biochemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001215378, proquestno: AAINN67642, Theses scanned by UMI/ProQuest. |
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