Growth hormone (GH) substitution in GH-deficient patients inhibits 11beta-hydroxysteroid dehydrogenase type 1 messenger ribonucleic acid expression in adipose tissue

Søren Kildeberg Paulsen, Steen Bønløkke Pedersen, Jens Otto Lunde Jørgensen, Sanne Fisker, Jens Sandahl Christiansen, Allan Flyvbjerg, Bjørn Richelsen

47 Citations (Scopus)

Abstract

CONTEXT: Local tissue activity of glucocorticoids is in part determined by the isoenzymes 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) and 11beta-HSD2, interconverting inert cortisone and active cortisol. Increased tissue activity of cortisol may play a central role in the features of GH deficiency and the metabolic syndrome.

OBJECTIVE: We investigated the effects of GH treatment on adipose tissue 11beta-HSD mRNA.

SUBJECTS AND METHODS: A randomized placebo-controlled double-blind study design was used. Twenty-three GH-deficient patients (16 males and seven females) were randomized to 4 months of GH treatment (2 IU/m2) (n = 11) or placebo treatment (n = 12). Adipose tissue biopsies and blood samples were obtained before and after treatment. Biopsies were obtained from the abdominal sc depot at the level of the umbilicus and do not necessarily reflect the metabolically more important visceral adipose tissue. Gene expressions were determined by real-time RT-PCR.

RESULTS: GH treatment decreased 11beta-HSD1 mRNA 66% [95% confidence interval (CI), 23-107%; P < 0.01] and increased 11beta-HSD2 mRNA 167% (95% CI, 33-297%; P < 0.05) in adipose tissue. Serum IGF-I and IGF-I mRNA increased in the GH-treated group by 187% (95% CI, 122-250%; P < 0.001) and 470% (95% CI, 88-846%; P < 0.01). The change in 11beta-HSD1 mRNA expression was negatively correlated with the change in serum IGF-I (R = -0.434; P < 0.05). In contrast, the change in 11beta-HSD2 mRNA expression was positively correlated with the change in serum IGF-I (R = 0.487; P < 0.05), and even stronger with the change in IGF-I mRNA expression (R = 0.798; P < 0.0001).

CONCLUSION: GH treatment is able to decrease 11beta-HSD1 mRNA and increase 11beta-HSD2 and accordingly may be able to reduce the amount of locally produced cortisol in adipose tissue.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Volume91
Issue number3
Pages (from-to)1093-8
Number of pages6
ISSN0021-972X
DOIs
Publication statusPublished - Mar 2006
Externally publishedYes

Keywords

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2
  • Adipose Tissue
  • Adult
  • Double-Blind Method
  • Female
  • Gene Expression Regulation
  • Gene Expression Regulation, Enzymologic
  • Human Growth Hormone
  • Humans
  • Hypopituitarism
  • Insulin-Like Growth Factor I
  • Male
  • Placebos
  • RNA, Messenger
  • Comparative Study
  • Journal Article
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

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