title: Inhibition of Pref-1 (preadipocyte factor 1) by oestradiol in adolescent girls with anorexia nervosa is associated with improvement in lumbar bone mineral density.
abstract: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  Sixty-nine girls (44 with AN, 25 normal-weight controls) 13-18 years were studied at baseline; 22 AN girls were followed prospectively.
  
  
  METHODS
  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: Neuroendocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, Boston, MA 02114, USA.
authors: Alexander T
authors: AT
authors: Faje
authors: Pouneh K
authors: PK
authors: Fazeli
authors: Debra
authors: D
authors: Katzman
authors: Karen K
authors: KK
authors: Miller
authors: Anne
authors: A
authors: Breggia
authors: Clifford J
authors: CJ
authors: Rosen
authors: Nara
authors: N
authors: Mendes
authors: Madhusmita
authors: M
authors: Misra
authors: Anne
authors: A
authors: Klibanski
mesh_terms: D000293:Adolescent; D000856:Anorexia Nervosa / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density; D002135:Calcium-Binding Proteins; D016022:Case-Control Studies; D002454:Cell Differentiation; D024042:Collagen Type I / Q000096:biosynthesis; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D015536:Down-Regulation; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008137:Longitudinal Studies; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000473:pathology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D010455:Peptides
chemical_list: D002135:Calcium-Binding Proteins; D024042:Collagen Type I; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D004958:Estradiol