Secretion of keratinocyte growth factor by cultured human endometrial stromal cells is induced through a cyclic adenosine monophosphate-dependent pathway.
OBJECTIVE
To evaluate the effects of known modulators of endometrial function on the production of keratinocyte growth factor by endometrial stromal cells.


METHODS
The effects of dibutyryl-cyclic adenosine monophosphate (db-cAMP), 12-O-tetradecanoylphorbol 13-acetate (TPA), ethinyl estradiol-17alpha (EE), and medroxyprogesterone acetate (MPA) on the secretion of keratinocyte growth factor by endometrial stromal cells were investigated.


METHODS
Research laboratory at a university medical school.


METHODS
Eleven endometrial specimens in the late proliferative phase.


METHODS
Endometrial stromal cells were incubated for 24 hours with db-cAMP, TPA, EE, or MPA.


METHODS
The concentration of keratinocyte growth factor in the culture media was measured using an ELISA.


RESULTS
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.


CONCLUSIONS
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.
Nasu
Kaei
K
Department of Obstetrics and Gynecology, Oita Medical University, Hasama-machi, Oita 879-5593, Japan. nasu@oita-med.ac.jp
Arima
Kazuyo
K
Fujisawa
Kayo
K
Nishida
Masakazu
M
Kai
Kengo
K
Miyakawa
Isao
I
D003994:Bucladesine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
D004791:Enzyme Inhibitors; C496453:FGF7 protein, human; D013873:Thionucleotides; D051523:Fibroblast Growth Factor 7; C016957:adenosine-3',5'-cyclic phosphorothioate; D004997:Ethinyl Estradiol; D005346:Fibroblast Growth Factors; D003994:Bucladesine; D017258:Medroxyprogesterone Acetate; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate