Background: A paucity of information exists concerning how estrogen affects cellular function in the gingiva of women. In this study, the behavior of human gingival fibroblasts was examined in the presence of a potent estrogen, estradiol.

Methods: Quiescent, premenopausal gingival fibroblasts were incubated in the presence and absence of estradiol (1 nM) and/or raloxifene (100 nM). Cell number was determined and cell cycle analyzed using a flow cytometer. Collagen and non‐collagen production in cell cultures grown on various extracellular matrices were determined using a radioactive microassay which measures collagenase‐digestible and collagenase‐resistant radiolabeled proteins. To ascertain if the gingiva contained specific estrogen‐sensitive cell populations, a fluorescence‐activated cell sorter was used to detect, sort, and enrich fibroblast populations responsive to estrogen.

Results: Cellular proliferation and the number of cells entering the S‐phase of the cell cycle were significantly increased in mass cultures of fibroblasts stimulated by estradiol. Raloxifene did not antagonize the action of estradiol on cell proliferation. In regard to protein production, estradiol significantly reduced collagen production on plastic and collagen IV matrices; whereas non‐collagen protein production on plastic and collagen I matrices was significantly reduced. Cell sorting of mass fibroblast populations revealed that, on average, 45% of the cells from the resident population selectively accumulated the estrogen probe. These sorted and estrogen‐sensitive enriched cell populations proliferated in the presence of 1 nM estradiol, whereas the sorted, estrogen‐deficient enriched fibroblast populations did not proliferate when incubated with 1 nM estradiol.

Conclusions: These data indicate that estradiol can induce cellular proliferation while depressing protein production in cultures of human, premenopausal gingival fibroblasts. This cellular proliferation appears to be the result of a specific population of cells within the parent culture that responds to physiologic concentrations of estradiol. J Periodontol 2005;76:1391‐1397.