Progesterone induces the fibulin-1 expression in human endometrial stromal cells.
BACKGROUND
By using microarray analysis with human endometrial stromal cells (ESCs), we previously reported that the mRNA for fibulin-1, an extracellular matrix as well as a plasma glycoprotein, is up-regulated by progesterone. In the present study, we tried to clarify the spatial and temporal regulation mechanism of fibulin-1 in the human endometrium.


RESULTS
Quantitative analysis with real-time PCR experiments on human endometrial tissues showed significantly higher fibulin-1 mRNA expressions in secretory phase endometria than in proliferative phase. Immunohistochemical studies revealed that the fibulin-1 protein is expressed in the glandular epithelium in proliferative phase endometria, and that expression switched to the stroma in secretory phase endometria. In culture experiments with ESCs, a significant increase of fibulin-1 mRNA expression was observed in cells treated with 6 alpha-methyl-17 alpha-hydroxy-progesterone acetate (MPA) or 8 bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP). MPA stimulated the fibulin-1 mRNA expression in a dose-dependent manner, and a progesterone antagonist, RU-486, inhibited the stimulatory effect almost completely. By contrast, beta-estradiol alone did not increase the fibulin-1 mRNA expression.


CONCLUSIONS
These results suggest that fiblin-1 is an important molecule that mediates progesterone action in human ESC differentiation towards implantation.
Nakamoto
T
T
Department of Obstetrics and Gynecology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8507, Japan. nakamott@takii.kmu.ac.jp
Okada
H
H
Nakajima
T
T
Ikuta
A
A
Yasuda
K
K
Kanzaki
H
H
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000328:Adult; D002135:Calcium-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D008597:Menstrual Cycle / Q000502:physiology*; D008875:Middle Aged; D015735:Mifepristone / Q000494:pharmacology; D011374:Progesterone / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism
D002135:Calcium-Binding Proteins; D006727:Hormone Antagonists; D012333:RNA, Messenger; C060820:fibulin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol; D017258:Medroxyprogesterone Acetate