17Β-ESTRADIOL AND PROGESTERONE UPREGULATE CYCLOOXYGENASE-2 EXPRESSION IN THE HUMAN GINGIVAL FIBROBLASTS

Gingivitis is associated with 60-75% of all pregnancies and elevated levels of 17β-estradiol and progesterone is known to increase gingival inflammation and the proinflammatory prostaglandins in the human gingiva. Since cyclooxygenase-2 (COX-2) is an inducible enzyme responsible for the production of prostaglandins at the sites of inflammation, it is plausible to hypothesize that 17β- estradiol and progesterone could contribute to gingival inflammation by upregulation of COX-2 expression and subsequent prostaglandin formation. To examine this hypothesis, primary cultures of human gingival fibroblasts (HGFs) from either sex were established. The cells were treated with different concentrations (10-5, 10-7, and 10-9 M) of 17β-estradiol and progesterone, and expression of COX-2 protein was detected immunocytochemically. The growth potential and proliferation of these cells were studied using trypan blue exclusion method and MTT assay. The results show that both 17β-estradiol and progesterone upregulate COX-2 expression in the HGFs significantly. In addition, progesterone is more effective than 17β-estradiol to induce COX-2 expression at 10-5M but not at lower concentration (10-9M). Furthermore, cells prepared from either sex do not show any difference in COX-2 expression following hormone treatment and neither hormones show any changes in proliferation of these cells. In conclusion, the results of this investigation clearly illustrate significant regulatory effects of 17β-estradiol and progesterone on COX-2 expression in the cultured HGFs. Thus, one possible pathogenetic mechanism of the female sex hormone-associated gingivitis in vivo may be the synthesis of proinflammatory prostaglandins via upregulation of COX-2 expression by gingiva in response to elevated levels of circulating estrogens and progesterone.