Document Detail

Divergent regulation of angiopoietin-1, angiopoietin-2, and vascular endothelial growth factor by hypoxia and female sex steroids in human endometrial stromal cells.
MedLine Citation:
PMID:  23352606     Owner:  NLM     Status:  Publisher    
OBJECTIVE: To investigate whether hypoxia or the female sex steroids exert direct effects on angiopoietin-1 (ANGPT1), ANGPT2, and vascular endothelial growth factor (VEGF) in human endometrial stromal cells (ESCs) to clarify the regulatory function of these local angiogenic factors in the endometrium. STUDY DESIGN: Human endometrial tissues were obtained from 18 patients aged 34-47 years undergoing hysterectomy for benign reasons. ESCs were cultured under hypoxic condition or treated with 17β-estradiol (E) and/or medroxyprogesterone acetate (MPA). The mRNA levels and production of ANGPT1, ANGPT2, and VEGF were assessed by real-time RT-PCR and ELISA, respectively. Analysis of hypoxia-inducible factor 1α (HIF-1α) and estrogen receptor α (ERα) protein levels were evaluated by Western blot analysis. RESULT(S): Hypoxia reduced the mRNA expression and protein production of ANGPT-1 in ESCs, whereas those of ANGPT2 were unaffected, resulting in an increase of the ANGPT2/ANGPT1 ratio. Hypoxia induced mRNA expression and protein production of VEGF. E simultaneously induced VEGF production and suppressed ANGPT1 production, resulting in an increase of the ANGPT2/ANGPT1 ratio. MPA or E+MPA reduced ANGPT2 production and sustained the levels of ANGPT1, resulting in a decrease of the ANGPT2/ANGPT1 ratio. With regard to the interaction of E and hypoxia, E did not affect the regulation of angiogenic factors, HIF-1α, and ERα under hypoxic conditions. CONCLUSIONS: Hypoxia and female sex hormones independently regulate the ANGPT2/ANGPT1 ratio and VEGF expression in human ESCs. These results may indicate a potential mechanism for hypoxia or female sex steroids influencing angiogenesis in the human endometrium.
Tomoko Tsuzuki; Hidetaka Okada; Hisayuu Cho; Kayo Shimoi; Hiroe Miyashiro; Katsuhiko Yasuda; Hideharu Kanzaki
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-24
Journal Detail:
Title:  European journal of obstetrics, gynecology, and reproductive biology     Volume:  -     ISSN:  1872-7654     ISO Abbreviation:  Eur. J. Obstet. Gynecol. Reprod. Biol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375672     Medline TA:  Eur J Obstet Gynecol Reprod Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan.
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