The effect of growth factors on the proliferation of human endometrial stromal cells in culture.
OBJECTIVE
Development of ectopic implants of endometriosis is associated with both an inflammatory response by macrophages and endometrial stromal cell proliferation. Macrophages are capable of releasing a variety of inflammatory mediators, including growth factors. To assess the impact of such factors on endometrial tissue, we have studied the effects of recombinant growth factors, fibroblast growth factor, epidermal growth factor, transforming growth factor-alpha, and inflammation mediators transforming growth factor-beta, and tumor necrosis factor-alpha on human endometrial stromal cell proliferation.


METHODS
Increasing concentrations of these compounds were added to cultures of primary, secondary, and long-term stromal cells and the cells were harvested at 24, 48, and 72 hours.


RESULTS
Epidermal growth factor, transforming growth factor-alpha, transforming growth factor-beta, and fibroblast growth factor induced a statistically significant, dose-dependent increase in stromal cell thymidine uptake of 1.5- to fivefold. The cytokine tumor necrosis factor had no effect alone, but the combination of fibroblast growth factor and tumor necrosis factor had a synergistic effect, increasing cell proliferation 25% to 84% over fibroblast growth factor alone.


CONCLUSIONS
The stromal cell response to a wide range of cell growth effectors and the potential of mediators like tumor necrosis factor-alpha to synergize suggest that such macrophage-secretory products may contribute to proliferation of endometrial implants in vivo.
Hammond
M G
MG
Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill 27599.
Oh
S T
ST
Anners
J
J
Surrey
E S
ES
Halme
J
J
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D004717:Endometrium / Q000166:cytology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D011994:Recombinant Proteins / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D015291:Transforming Growth Factors / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D006133:Growth Substances; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D013936:Thymidine