title: Lack of regulation of 11beta-hydroxysteroid dehydrogenase type 1 during short-term manipulation of GH in patients with hypopituitarism.
abstract: OBJECTIVE
  Evidence from long-term clinical studies measuring urinary steroid ratios, and from in vitro studies, suggests that GH administered for longer than 2 months down-regulates 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), thereby reducing cortisol regeneration in liver and adipose tissue. We aimed to measure acute effects of GH on 11beta-HSD1 in liver and adipose tissue in vivo, including using a stable isotope tracer.
  
  
  METHODS
  Observational studies of GH withdrawal and reintroduction in patients with hypopituitarism.
  
  
  METHODS
  Twelve men with benign pituitary disease causing GH and ACTH deficiency on stable replacement therapy for >6 months were studied after GH withdrawal for 3 weeks, and after either placebo or GH injections were reintroduced for another 3 weeks. We measured cortisol kinetics during 9,11,12,12-(2)H(4)-cortisol (d4-cortisol) infusion, urinary cortisol/cortisone metabolite ratios, liver 11beta-HSD1 by appearance of plasma cortisol after oral cortisone, and 11beta-HSD1 mRNA levels in subcutaneous adipose biopsies.
  
  
  RESULTS
  GH withdrawal and reintroduction had no effect on 9,12,12-[(2)H](3)-cortisol (d3-cortisol) appearance, urinary cortisol/cortisone metabolite ratios, initial appearance of cortisol after oral cortisone, or adipose 11beta-HSD1 mRNA. GH withdrawal increased plasma cortisol 30-180 min after oral cortisone, increased d4-cortisol clearance, and decreased relative excretion of 5alpha-reduced cortisol metabolites.
  
  
  CONCLUSIONS
  In this setting, GH did not regulate 11beta-HSD1 rapidly in vivo in humans. Altered cortisol metabolism with longer term changes in GH may reflect indirect effects on 11beta-HSD1. These data do not suggest that glucocorticoid replacement doses need to be increased immediately after introducing GH therapy to compensate for reduced 11beta-HSD1 activity, although dose adjustment may be required in the longer term.
authors: Department of Endocrinology and Metabolism, Sahlgrenska Academy, Gothenburg University, Sahlgrenska University Hospital, Gröna stråket 8, 413 45 Göteborg, Sweden. helga.sigurjonsdottir@gu.se
authors: Helga A
authors: HA
authors: Sigurjonsdottir
authors: Ruth
authors: R
authors: Andrew
authors: Roland H
authors: RH
authors: Stimson
authors: Gudmundur
authors: G
authors: Johannsson
authors: Brian R
authors: BR
authors: Walker
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics* / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D000368:Aged; D054796:Drug Dosage Calculations; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007018:Hypopituitarism / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000652:urine; D008297:Male; D008875:Middle Aged; D010919:Placebos; D013997:Time Factors; D028761:Withholding Treatment; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D010919:Placebos; D019382:Human Growth Hormone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D006854:Hydrocortisone