GH effect on enzyme activity of 11βHSD in abdominal obesity is dependent on treatment duration

Objective: In the past years the interaction of GH and 11bhydroxysteroid dehydrogenase (11bHSD) in the pathogenesis of central obesity has been suggested. Design: We studied the effects of 9 months of GH treatment on 11bHSD activity and its relationship with body composition and insulin sensitivity in 30 men with abdominal obesity, aged 48 – 66 years, in a randomised, double-blind, placebo-controlled trial. Methods: Urinary steroid profile was used to estimate 11bHSD type 1 and 2 (11bHSD1 and 11bHSD2) activities. Abdominal s.c. and visceral adipose tissues were measured using computed tomography. Glucose disposal rate (GDR) obtained during a euglycaemic – hyperinsulinaemic glucose clamp was used to assess insulin sensitivity. Results: In the GH-treated group the 11bHSD1 activity decreased transiently after 6 weeks (P , 0.01) whereas 11bHSD2 increased after 9 months of treatment (P , 0.05). Between 6 weeks and 9 months, GDR increased and visceral fat mass decreased. Changes in 11bHSD1 correlated with changes in visceral fat mass between baseline and 6 weeks. There were no significant correlations between 11bHSD1 and 11bHSD 2 and changes in GDR. Discussion: The study demonstrates that short- and long-term GH treatment has different effects on 11bHSD1 and 11bHSD2 activity. Moreover, the data do not support that long-term metabolic effects of GH are mediated through its action on 11bHSD.