Document Detail


Inhibition of Pref-1 (preadipocyte factor 1) by oestradiol in adolescent girls with anorexia nervosa is associated with improvement in lumbar bone mineral density.
MedLine Citation:
PMID:  23331192     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Adolescents with anorexia nervosa (AN) are amenorrheic and have decreased bone mass accrual and low bone mineral density (BMD). The regulation of mesenchymal stem cell differentiation is an important factor governing bone formation. Preadipocyte factor 1 (Pref-1), an inhibitor of adipocyte and osteoblast differentiation, is elevated in states of oestrogen deficiency. In this study, we aim to (i) investigate effects of transdermal oestradiol on Pref-1 in adolescent girls with AN, and (ii) examine associations of changes in Pref-1 with changes in lumbar BMD and bone turnover markers.
DESIGN: Adolescent girls with AN and normal-weight controls were studied cross-sectionally. Girls with AN were examined longitudinally in a double-blind study and received transdermal oestradiol (plus cyclic medroxyprogesterone) or placebo for 12 months.
PATIENTS: Sixty-nine girls (44 with AN, 25 normal-weight controls) 13-18 years were studied at baseline; 22 AN girls were followed prospectively.
MEASUREMENTS: Pref-1 levels, bone formation and resorption markers, and BMD.
RESULTS: Pref-1 levels decreased in girls with AN after treatment with transdermal oestradiol compared with placebo (-0·015 ± 0·016 vs 0·060±0·026 ng/ml, P = 0·01), although at baseline, levels did not differ in AN vs controls (0·246 ± 0·015 vs 0·267 ± 0·022 ng/ml). Changes in Pref-1 over 12 months correlated inversely with changes in lumbar BMD (r = -0·48, P = 0·02) and positively with changes in CTX (r = 0·73, P = 0·006).
CONCLUSIONS: For the first time, we show that Pref-1 is negatively regulated by oestradiol in adolescent girls with AN. Inhibition of Pref-1 may mediate the beneficial effects of transdermal oestradiol replacement on BMD in girls with AN.
Authors:
Alexander T Faje; Pouneh K Fazeli; Debra Katzman; Karen K Miller; Anne Breggia; Clifford J Rosen; Nara Mendes; Madhusmita Misra; Anne Klibanski
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural     Date:  2013-07-02
Journal Detail:
Title:  Clinical endocrinology     Volume:  79     ISSN:  1365-2265     ISO Abbreviation:  Clin. Endocrinol. (Oxf)     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-07-24     Completed Date:  2014-02-24     Revised Date:  2014-09-02    
Medline Journal Info:
Nlm Unique ID:  0346653     Medline TA:  Clin Endocrinol (Oxf)     Country:  England    
Other Details:
Languages:  eng     Pagination:  326-32     Citation Subset:  IM    
Copyright Information:
© 2013 John Wiley & Sons Ltd.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Anorexia Nervosa / metabolism*
Body Weight / drug effects
Bone Density
Case-Control Studies
Cell Differentiation
Collagen Type I / biosynthesis
Cross-Sectional Studies
Double-Blind Method
Down-Regulation
Estradiol / pharmacology*
Female
Gene Expression Regulation*
Humans
Intercellular Signaling Peptides and Proteins / metabolism*
Longitudinal Studies
Lumbar Vertebrae / drug effects,  pathology*
Membrane Proteins / antagonists & inhibitors*,  metabolism*
Mesenchymal Stromal Cells / cytology
Peptides
Grant Support
ID/Acronym/Agency:
1 UL1 RR025758-01/RR/NCRR NIH HHS; R01 DK062249/DK/NIDDK NIH HHS; R01 DK062249/DK/NIDDK NIH HHS; R24 DK092759/DK/NIDDK NIH HHS; UL1 RR025758/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Collagen Type I; 0/DLK1 protein, human; 0/Intercellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/Peptides; 0/collagen type I trimeric cross-linked peptide; 4TI98Z838E/Estradiol
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