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


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).


CONCLUSIONS
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.
Paulsen
Søren Kildeberg
SK
Department of Endocrinology and Metabolism C, Aarhus University Hospital, Aarhus Sygehus, Tage Hansensgade 2, DK-8000 Aarhus C, Denmark. skpaulsen@dadlnet.dk
Pedersen
Steen Bønløkke
SB
Jørgensen
Jens Otto Lunde
JO
Fisker
Sanne
S
Christiansen
Jens Sandahl
JS
Flyvbjerg
Allan
A
Richelsen
Bjørn
B
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics; D000273:Adipose Tissue / Q000201:enzymology*; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D007018:Hypopituitarism / Q000188:drug therapy / Q000201:enzymology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008297:Male; D010919:Placebos; D012333:RNA, Messenger / Q000235:genetics*
D010919:Placebos; D012333:RNA, Messenger; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2