Changes in the Expression Pattern of Cyclooxygenase-2, Mapkinases and Related Apoptotic Markers by Different Levels of Estrogen Supplementation in Mature or Ovariectomized Female Rat Heart

Shin, Jang In; Park, Ock Jin

Abstract

The effects of different concentrations of estrogen supplementation to mature female rats or estrogen supplementation to ovariectomized rats on cyclooxygenase-2 (COX-2) expression, PGE2 production and mapkinases expression were investigated in experimentally induced atherogenic rats with feeding a high fat.high cholesterol diet. In the first experiment using 48-week old mature rats, the supplementation of three different levels of estrogen was compared to the basal diet. The high concentration of estrogen supplementation induced the marked up-regulation of COX-2 protein and the increase in plasma PGE2 production and this seems to be followed by the up-regulation of p38 among mapkinases. The regulation of bax showed in a reverse trend of COX-2 in heart tissues of mature female rats. In the second experimental system, female Sprague-Dawley rats were bilaterally ovariectomized; sham-operated animals were used as controls. Three weeks later, the animals were supplied with basal diet to sham-operated control group and ovariectomized control group, and estrogen supplemented diet to ovariectomized group for an eight-week experimental period. In a group supplemented with a medium dose of estrogen, COX-2 expression was up-regulated. This up-regulation was accompanied by the elevated expression of pERK1/2. Bax was increased in estrogen-fed animals indicating bax might be involved in estrogen feeding state in ovariectomized rats. Further investigations on the relationship between COX-2 and biological activities such as vasodilation by estrogen are required in in vivo system of female rats at the various physiological states.