Endocrine Abstracts (2002) 3 P263

Growth hormone increases fat mass in patients with simple obesity

JW Tomlinson1, N Crabtree2, PMS Clark3, G Holder3, CHL Shackleton4 & PM Stewart1


1Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK; 2Department of Nuclear Medicine, Queen Elizabeth Hospital, Birmingham, UK; 3Regional Endocrine Laboratory, Department of Clinical Biochemistry, University Hospital Birmingham, Birmingham, UK; 4Children's Hospital, Oaklands Research Institute, California, USA.


Patients with obesity are relatively Growth Hormone (GH) deficient. GH has potent effects on adipocyte biology, stimulating lipolysis but also promoting pre-adipocyte proliferation. Conversely, we have shown that cortisol inhibits pre-adipocyte proliferation and enhances differentiation. Furthermore, GH, acting through IGF-1, inhibits 11 beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) which converts the inactive glucocorticoid, cortisone (E) to active cortisol (F) in adipose tissue. Previous studies treating obese patients with GH have been for short periods with large doses; consequently, the incidence of side effects has been high.

We conducted a randomised, double-blind placebo controlled study using low dose GH (Genotropin 1.2iu/day) for 8 months in patients with obesity. 24 adult patients (11 men, 13 women, mean BMI 36.4±1.1kg/m2, mean ± SE) were randomly assigned to treatment or placebo.

IGF-1 was significantly elevated in the GH treatment group (e.g. 4 months: 51.0±6.4 vs. 17.9±1.8nmol/l, p<0.001). Total fat mass (assessed by dual energy x-ray absorptiometry) significantly increased in the GH treated group (41.0±2.4 vs. 42.6±3.5kg, p<0.05 vs. baseline). In addition, insulin sensitivity decreased (fasting glucose: insulin ratio 0.06±0.01 vs. 0.04±0.01, p=0.05 vs baseline) and systolic blood pressure increased (119±3 vs. 130±4mmHg, p<0.05 vs. baseline). There was no alteration in fasting lipids or anthropometric measurements. 11beta-HSD1 activity (assessed by urinary tetrahydrometabolites of E and F, THF+alloTHF: THE) was inhibited in the GH treated group (1.22±0.14 vs 1.09±0.14, p=0.07 vs baseline). Similarly, serum F: E ratio also decreased significantly (6.1±0.4 vs. 4.4±0.5, p<0.01 vs. baseline).

Treatment with low dose GH in obesity caused a significant increase in fat mass. It is possible that at low doses of GH, pre-adipocyte proliferation occurs preferentially to lipolysis. In addition, inhibition of 11beta-HSD1 in adipose tissue may reduce the availability of cortisol to bind to the glucocorticoid receptor and thus enhance pre-adipocyte proliferation.

This work was supported by a research grant from Pharmacia and Upjohn.

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