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FKBP52 is regulated by HOXA10 during decidualizaton and in endometriosis.
MedLine Citation:
PMID:  22279148     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
FKBP52 and FKBP51 are progestin receptor (PR) co-chaperone protein that enhance and inhibit, respectively, progestin-mediated transcription by PR. Here we examined FKBP52 and FKBP51 expression in eutopic endometrium of fertile women and those with endometriosis, the effects FKBP52 and FKBP51 on the decidualization of human endometrial stromal cells (HESCs) and assessed HOXA10 regulation of FKBP52. Expression of FKBP52 mRNA was increased in the late proliferative phase and remained elevated through the secretory phase. FKBP51 expression was low and remained constant throughout the menstrual cycle. Compared with controls, FKBP52 mRNA expression was decreased in endometrium from women with endometriosis, whereas no significant endometriosis-related change was seen for FKBP51. Cultured HESCs were treated with either FKBP52 or FKBP51 siRNA then decidualized by incubation with progesterone and 8-Bromoadenosine 3', 5'-cyclic monophosphate (cAMP). FKBP52 siRNA treatment of HESCs resulted in 60% lower IGFBP-1 expression. By contrast, incubation with FKBP51 siRNA did not significantly decrease IGFBP-1 expression during in vitro decidualization. HOXA10 and FKBP52 expression increased in parallel during in vitro decidualization. In HESC over-expressed HOXA10 enhanced FKBP52 mRNA and protein levels, whereas HOXA10 knock-down decreased FKBP52 mRNA and protein compared to controls. Similarly, during in vitro decidualization, FKBP52 expression was decreased in HOXA10 silenced cells. Enhanced HOXA10 expression in HESCs elicits a decidualization mediating increase in FKBP52 expression. The findings are consistent with the observation that women with endometriosis have diminished FKBP52 expression leading to impaired decidualization and infertility. The progesterone resistance seen in endometriosis may be mediated through HOXA10 regulated FKBP52 expression.
Authors:
Huan Yang; Yuping Zhou; Benjiamin Edelshain; Frederick Schatz; Charles J Lockwood; Hugh S Taylor
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-25
Journal Detail:
Title:  Reproduction (Cambridge, England)     Volume:  -     ISSN:  1741-7899     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100966036     Medline TA:  Reproduction     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
H Yang, OB/GYN, Yale, New Haven, United States.
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