Document Detail


FKBP52 deficiency-conferred uterine progesterone resistance is genetic background and pregnancy stage specific.
MedLine Citation:
PMID:  17571166     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Immunophilin FKBP52 serves as a cochaperone to govern normal progesterone (P(4)) receptor (PR) function. Using Fkbp52(-/-) mice, we show intriguing aspects of uterine P(4)/PR signaling during pregnancy. Implantation failure is the major phenotype found in these null females, which is conserved on both C57BL6/129 and CD1 backgrounds. However, P(4) supplementation rescued implantation and subsequent decidualization in CD1, but not C57BL6/129, null females. Surprisingly, experimentally induced decidualization in the absence of blastocysts failed in Fkbp52(-/-) mice on either background even with P(4) supplementation, suggesting that embryonic signals complement uterine signaling for this event. Another interesting finding was that while P(4) at higher than normal pregnancy levels conferred PR signaling sufficient for implantation in CD1 null females, these levels were inefficient in maintaining pregnancy to full term. However, elevating P(4) levels further restored PR signaling to a level optimal for successful term pregnancy with normal litter size. Collectively, the results show that the indispensability of FKBP52 in uterine P(4)/PR signaling is a function of genetic disparity and is pregnancy stage specific. Since there is evidence for a correlation between P(4) supplementation and reduced risks of P(4)-resistant recurrent miscarriages and remission of endometriosis, these findings have clinical implications for genetically diverse populations of women.
Authors:
Susanne Tranguch; Haibin Wang; Takiko Daikoku; Huirong Xie; David F Smith; Sudhansu K Dey
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  117     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-07-03     Completed Date:  2007-09-18     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1824-34     Citation Subset:  AIM; IM    
Affiliation:
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232-2678, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blastocyst / drug effects,  metabolism
Drug Resistance*
Embryo Transfer
Female
Mice
Mice, Knockout
Pregnancy
Progesterone / pharmacology*
Receptors, Progesterone / metabolism
Signal Transduction
Tacrolimus Binding Proteins / deficiency*,  genetics,  metabolism*
Uterus / drug effects*,  metabolism*
Grant Support
ID/Acronym/Agency:
DK48218/DK/NIDDK NIH HHS; F31 DA021062/DA/NIDA NIH HHS; HD033994/HD/NICHD NIH HHS; HD050315/HD/NICHD NIH HHS; HD12304/HD/NICHD NIH HHS; T32 DK07563/DK/NIDDK NIH HHS; U54 HD28934/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Progesterone; 57-83-0/Progesterone; EC 5.2.1.-/Tacrolimus Binding Proteins; EC 5.2.1.-/tacrolimus binding protein 4
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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