Regulated expression of prostaglandin endoperoxide synthase-2 by uterine stroma

Andrew L. Jacobs, Daniel Hwang, Joanne Julian, Daniel D. Carson

Research output: Contribution to journalArticle

Abstract

Our previous studies demonstrated that interleukin-1 α (IL-1 α) 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 α- and UEC-induced PGE2 secretion by cycloheximide and actinomycin-D in the presence of a saturating concentration of arachidonic acid indicated that IL-1 α 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 α, UEC-conditioned medium, or serum. Inhibition of UEC-stimulated PGHS-2 expression by anti-IL-1 α indicated that IL-1 α 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 α- 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 α 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.

Original languageEnglish (US)
Pages (from-to)1807-1815
Number of pages9
JournalEndocrinology
Volume135
Issue number5
DOIs
StatePublished - 1994
Externally publishedYes

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Prostaglandin-Endoperoxide Synthases
Cyclooxygenase 2
Stromal Cells
Interleukin-1
Epithelial Cells
Prostaglandins
Dinoprostone
Dexamethasone
Dactinomycin
Blastocyst
Cycloheximide
Conditioned Culture Medium
Mitogens
Arachidonic Acid
Protein Isoforms
Western Blotting
Membranes
Enzymes
Serum

ASJC Scopus subject areas

  • Endocrinology

Cite this

Regulated expression of prostaglandin endoperoxide synthase-2 by uterine stroma. / Jacobs, Andrew L.; Hwang, Daniel; Julian, Joanne; Carson, Daniel D.

In: Endocrinology, Vol. 135, No. 5, 1994, p. 1807-1815.

Research output: Contribution to journalArticle

Jacobs, Andrew L. ; Hwang, Daniel ; Julian, Joanne ; Carson, Daniel D. / Regulated expression of prostaglandin endoperoxide synthase-2 by uterine stroma. In: Endocrinology. 1994 ; Vol. 135, No. 5. pp. 1807-1815.
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abstract = "Our previous studies demonstrated that interleukin-1 α (IL-1 α) 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 α- and UEC-induced PGE2 secretion by cycloheximide and actinomycin-D in the presence of a saturating concentration of arachidonic acid indicated that IL-1 α 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 α, UEC-conditioned medium, or serum. Inhibition of UEC-stimulated PGHS-2 expression by anti-IL-1 α indicated that IL-1 α 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 α- 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 α 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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