title: Diminished 11β-hydroxysteroid dehydrogenase type 2 activity is associated with decreased weight and weight gain across the first year of life.
abstract: BACKGROUND
  Low birth weight is associated with adverse metabolic outcome in adulthood. Exposure to glucocorticoid (GC) excess in utero is associated with decreased birth weight, but the prospective longitudinal relationship between GC metabolism and growth has not been examined.
  
  
  OBJECTIVE
  We have hypothesized that changes in GC metabolism leading to increased availability may impair growth.
  
  
  METHODS
  This was a prospective, longitudinal study with clinical measurements and 24-hour urinary steroid metabolite analysis at 1, 4, 12, 26, and 52 weeks after delivery in mothers and their babies.
  
  
  METHODS
  The study was conducted with observations and samples collected in the volunteers' own homes.
  
  
  METHODS
  Healthy mothers and newborn babies/infants participated in the study.
  
  
  METHODS
  There were no interventions.
  
  
  METHODS
  Urinary steroid metabolite excretion quantified by gas chromatography/mass spectroscopy across the first year of life in relation to change in weight was measured.
  
  
  RESULTS
  The total production of the GC metabolites quantified increased across the first year of life. Markers of 11β-hydroxysteroid dehydrogenase type 1 activity increased from the age of 3 months as did those of 5α-reductase activity. After correcting for confounding variables, low markers of 11β-hydroxysteroid dehydrogenase type 2 activity was associated with reduced absolute weight and decreased weight gain over the first year of life. In the mothers, 5α-reductase activity was low at birth and progressively increased to normal over the first 6 months postpartum.
  
  
  CONCLUSIONS
  Increased GC exposure as a consequence of reduced 11β-hydroxysteroid dehydrogenase type 2 activity is likely to be a critical determinant of growth in early life. This not only highlights the central role of GCs and their metabolism, but also emphasizes the need for detailed longitudinal analyses.
authors: School of Psychology (S.L.R., C.A.J., L.F., K.S., J.B.) and Centre for Endocrinology, Diabetes, and Metabolism (B.A.H., P.M.S., C.H.L.S., N.P.K., J.W.T.), Institute of Biomedical Research, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TH, United Kingdom; Department of Clinical Biochemistry (N.T.), King's College Hospital National Health Service Foundation Trust, London WC2R 2LS, United Kingdom; and Children's Hospital, Oakland's Research Institute (C.H.L.S.), Oakland, California 94609.
authors: Samantha L
authors: SL
authors: Rogers
authors: Beverly A
authors: BA
authors: Hughes
authors: Christopher A
authors: CA
authors: Jones
authors: Lauren
authors: L
authors: Freedman
authors: Katherine
authors: K
authors: Smart
authors: Norman
authors: N
authors: Taylor
authors: Paul M
authors: PM
authors: Stewart
authors: Cedric H L
authors: CH
authors: Shackleton
authors: Nils P
authors: NP
authors: Krone
authors: Jacqueline
authors: J
authors: Blissett
authors: Jeremy W
authors: JW
authors: Tomlinson
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism*; D001835:Body Weight / Q000502:physiology*; D002657:Child Development / Q000502:physiology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011446:Prospective Studies; D015430:Weight Gain / Q000502:physiology*
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2