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Publication : Regulated expression of prostaglandin endoperoxide synthase-2 by uterine stroma.

First Author  Jacobs AL Year  1994
Journal  Endocrinology Volume  135
Issue  5 Pages  1807-15
PubMed ID  7956904 Mgi Jnum  J:21589
Mgi Id  MGI:69525 Doi  10.1210/endo.135.5.7956904
Citation  Jacobs AL, et al. (1994) Regulated expression of prostaglandin endoperoxide synthase-2 by uterine stroma. Endocrinology 135(5):1807-15
abstractText  Our previous studies demonstrated that interleukin-1 alpha (IL-1 alpha) and soluble factors secreted by polarized uterine luminal epithelial cells (UEC) stimulate prostaglandin (PG) secretion by uterine stromal cells (USC). The present studies were aimed at determining the mechanism by which these agonists stimulate PG secretion by USC. The comoplete inhibition of IL-1 alpha- and UEC-induced PGE2 secretion by cycloheximide and actinomycin-D in the presence of a saturating concentration of arachidonic acid indicated that IL-1 alpha and UEC act to a large extent by inducing de novo expression of PG endoperoxide synthase (PGHS). Western blot analysis of membrane fractions from USC showed a 2- to 4-fold accumulation of the mitogen-inducible isoform of PGHS (PGHS-2), but not the constitutively expressed enzyme (PGHS-1), within 3 h of treatment with IL-1 alpha, UEC-conditioned medium, or serum. Inhibition of UEC-stimulated PGHS-2 expression by anti-IL-1 alpha indicated that IL-1 alpha is one factor secreted by UEC responsible for the synthesis of USC PGHS-2. Expression of PGHS-2, but not PGHS-1, was inhibited by dexamethasone. Dexamethasone also inhibited IL-1 alpha- and UEC-stimulated PGE2 secretion by USC. Immunohistochemical studies demonstrated that PGHS-2 is localized to implantation sites in newly differentiating USC at the time of blastocyst attachment, indicating a potential physiological role for PGHS-2 in early stages of mouse implantation. In contrast, PGHS-1 was localized to UEC during this period. Collectively, these results indicate that enhanced PG secretion by USC in response to IL-1 alpha and soluble factors secreted by UEC is due to selective expression of PGHS-2. In addition, the expression of PGHS-2 by USC in vivo during the periimplantation period may support PG secretion required during early stages of embryo implantation.
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