Regulation of COX-2 gene expression in rat uterus in vivo and in vitro

https://doi.org/10.1016/S0090-6980(96)00125-6Get rights and content

Abstract

Prostaglandins are involved in mediating several important processes in mammalian reproduction, including the initiation of parturition. In the present study, we examined the expression in the rat uterus of two-rate limiting enzymes involved in prostaglandin production, cyclooxygenase (COX) 1 and 2. Expression of the COX-2 gene in the pregnant rat uterus gave rise to a single mRNA transcript of approximately 4.4 kb. COX-2 mRNA levels increased 3.5 fold between day 7 of pregnancy and the onset of parturition on day 22. In contrast, COX-1 mRNA levels remained constant during the same period. To investigate factors involved in mediating the regulation of COX-1 and COX-2 gene expression, rat endometrial stromal and epithelial cell lines, were used. In the stroma-derived cell line, CUS-V2, COX-2 gene expression was demonstrated by reverse transcriptase/polymerase chain reaction (RT-PCR) and by immunocytochemistry. In these cells, COX-2 gene expression was inducible by the cytokines interleukin-1 β and tumor necrosis factor α, but not by interleukin-6. The two former cytokines also induced prostaglandin F production. In contrast, COX-1 gene expression was constitutive in this cell line. In the endometrial epithelium-derived cell line, CUE-P both COX-1 and COX-2 genes were expressed in a constitutive fashion. In conclusion, the present in vivo and in vitro data indicate that decidual COX-2, but not COX-1, gene expression is regulated during pregnancy and implicate specific cytokines as possible inducers within the decidua.

References (59)

  • K. Bry et al.

    Transforming growth factor-B opposes the stimulatory effects of interleukin-1 and tumor necrosis factor on amnion cell prostaglandin E2 production: Implications for preterm labor

    Am. J. Obstet. Gynecol.

    (1992)
  • L. Feng et al.

    Cloning two isoforms of rat cyclooxygenase: differential regulation of their expression

    Arch. Biochem. Biophys.

    (1993)
  • S.H. Lee et al.

    Selective expression of mitogeninducible cyclooxygenase in macrophage stimulated with lipopolysaccharide

    J. Biol. Chem.

    (1992)
  • K.P. Crookston et al.

    Classification of α-2 macroglobulin-cytokine interactions based on affinity of non-covalent association in solution under apparent equilibrium conditions

    J. Biol. Chem.

    (1994)
  • P.Y.C. Cheung et al.

    Immunocytochemical distribution and localization of 15-hyroxyprostaglandin dehydrogenase in human fetal membranes, decidua, and placenta

    Am. J. Obstet. Gynecol.

    (1990)
  • M.L. Casey et al.

    NAD+-dependent 15-hydroxyprostaglandin dehydrogenase activity in human endometrium

    Prostaglandins

    (1980)
  • M.J.N.C. Keirse et al.

    Increase in placental 15-hydroxyprostaglandin dehydrogenase in the first half of human pregnancy

    Prostaglandins

    (1985)
  • P. Husslein et al.

    Oxytocin and the initiation of human parturition

    Am. J. Obstet. Gynecol.

    (1981)
  • S.A. Jones et al.

    Local stimulation of prostaglandin production by corticotropin-releasing hormone in human fetal membranes and placenta

    Biochem. Biophys. Res. Commun.

    (1989)
  • R. Langenbach et al.

    Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration

    Cell

    (1995)
  • H.R. Behrman et al.
  • R.W. Kelley

    Pregnancy maintenance and parturition: the role of prostaglandins in manipulating the immune and inflammatory response

    Endoc. Rev.

    (1994)
  • S. Greenberg
  • D.M. Olson et al.

    Prostaglandins and parturition

    Prog. Endocrinol.

    (1992)
  • R.J. Romero et al.
  • M. Alexandrova et al.

    Oxytocin receptors and parturition. IIII. Increases in estrogen receptor and oxytocin receptor concentrations in the rat myometrium during prostaglandin F-induced abortion

    Endocrinology

    (1980)
  • F.R. Blatchley et al.

    Luteolytic effect of prostaglandin in the guineapig

    Nature

    (1969)
  • R.J. Mayer et al.

    New insights on mammalian phospholipase A2: comparison of arachidonyl-selective and non-selective enzymes

    FASEB J.

    (1993)
  • Cited by (0)

    View full text