Secretion of keratinocyte growth factor by cultured human endometrial stromal cells is induced through a cyclic adenosine monophosphate-dependent pathway

Abstract

Objective: To evaluate the effects of known modulators of endometrial function on the production of keratinocyte growth factor by endometrial stromal cells. Design: The effects of dibutyryl-cyclic adenosine monophosphate (db-cAMP), 12- O-tetradecanoylphorbol 13-acetate (TPA), ethinyl estradiol-17α (EE), and medroxyprogesterone acetate (MPA) on the secretion of keratinocyte growth factor by endometrial stromal cells were investigated. Setting: Research laboratory at a university medical school. Patient(s): Eleven endometrial specimens in the late proliferative phase. Intervention(s): Endometrial stromal cells were incubated for 24 hours with db-cAMP, TPA, EE, or MPA. Main Outcome Measure(s): The concentration of keratinocyte growth factor in the culture media was measured using an ELISA. Result(s): Small amounts of keratinocyte growth factor were detected in the culture media of unstimulated endometrial stromal cells. The production of keratinocyte growth factor by endometrial stromal cells was stimulated with db-cAMP in a dose-dependent manner. The stimulatory effect of db-cAMP was inhibited by Rp-adenosine 3′,5′-cyclic monophosphothioate. None of TPA, EE, nor MPA affected the keratinocyte growth factor production by these cells. Conclusion(s): These results suggest that a cAMP-dependent pathway may play an important role in the regulation of keratinocyte growth factor production by endometrial stromal cells. Keratinocyte growth factor secreted by endometrial stromal cells may be involved in the regeneration of the endometrium during the normal menstrual cycle and early pregnancy.