Context: Local tissue activity of glucocorticoids is in part determined by the isoenzymes 11-HSD1 and 11-HSD2, interconverting inert cortisone and active cortisol. Increased tissue activity of cortisol may play a central role in the features of growth hormone deficiency (GHD) and the metabolic syndrome.

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

Subjects and methods: A randomized placebo-controlled double-blind study design was used. 23 GHD patients (16M, 7F) were randomized to four 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 11-HSD1 mRNA 66% (95% C.I: 23%-107%, P < 0.01) and increased 11-HSD2 mRNA 167% (95% C.I: 33%-297%, P < 0.05) in adipose tissue. Serum-IGF-I and IGF-I mRNA increased in the GH-treated group by 187% (95% C.I: 122%-250%, P < 0.001), and 470% (95% C.I: 88%-846%, P < 0.01). The change in 11-HSD1 mRNA expression was negatively correlated with the change in serum-IGF-I (R0.434, P < 0.05). In contrast, the change in 11-HSD2 mRNA expression was positively correlated to the change in serum-IGF-I (R=0.487, P < 0.05), and even stronger to the change in IGF-I mRNA expression (R=0,798, P < 0.0001).

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