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Growth Hormone (GH) Substitution in GH-Deficient Patients Inhibits 11ß-Hydroxysteroid Dehydrogenase Type 1 Messenger Ribonucleic Acid Expression in Adipose Tissue

Department of Endocrinology and Metabolism C (S.K.P., S.B.P., S.F., B.R.), Medical Department M (Diabetes and Endocrinology) (J.O.L.J., J.S.C.), and The Medical Research Laboratories (A.F.), Clinical Institute and Medical Department M (Diabetes and Endocrinology), Aarhus University Hospital, Aarhus Sygehus, DK-8000 Aarhus C, Denmark

Address all correspondence and requests for reprints to: Søren K. Paulsen, Department of Endocrinology and Metabolism C, Aarhus University Hospital, Aarhus Sygehus, Tage Hansensgade 2, DK-8000 Aarhus C, Denmark. E-mail: skpaulsen{at}dadlnet.dk.

Context: Local tissue activity of glucocorticoids is in part determined by the isoenzymes 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) and 11ß-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 11ß-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 11ß-HSD1 mRNA 66% [95% confidence interval (CI), 23–107%; P < 0.01] and increased 11ß-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 11ß-HSD1 mRNA expression was negatively correlated with the change in serum IGF-I (R = –0.434; P < 0.05). In contrast, the change in 11ß-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 11ß-HSD1 mRNA and increase 11ß-HSD2 and accordingly may be able to reduce the amount of locally produced cortisol in adipose tissue.

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