Low-dose growth hormone inhibits 11 beta-hydroxysteroid dehydrogenase type 1 but has no effect upon fat mass in patients with simple obesity.
GH has potent effects on adipocyte biology, stimulating lipolysis but also promoting preadipocyte proliferation. In addition, GH, acting through IGF-I, inhibits 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1), which converts the inactive glucocorticoid, cortisone (E), to active cortisol (F) in adipose tissue. Although F is an essential requirement for adipocyte differentiation, it also inhibits preadipocyte proliferation. We hypothesized that inhibition of 11 beta-HSD1 activity in adipose tissue by GH may alter fat tissue mass through changes in local F concentrations. We conducted a randomized, double-blind, placebo-controlled study using low-dose GH (Genotropin 0.4 mg/d) for 8 months in 24 patients with obesity. Although GH treatment significantly raised IGF-I, we were unable to demonstrate significant differences in body composition or metabolic profiles between GH- and placebo-treated groups. In addition, there was no alteration in total fat mass over time in the GH-treated group [total fat mass 41.0 +/- 3.0 vs. 41.3 +/- 3.4 kg (8 months), mean +/- SE, P = ns]. However, in comparison with baseline values, systolic blood pressure increased (119 +/- 3 vs. 130 +/- 4 mm Hg, P < 0.05 vs. baseline) and serum F/E ratio decreased (6.1 +/- 0.5 vs. 3.9 +/- 0.5, P < 0.05 vs. baseline) in the GH-treated group only. Furthermore, although the urinary tetrahydrometabolites of F/E ratio fell in the GH-treated group, it rose in the placebo group (mean ratio change, -0.13 +/- 0.05 vs. +0.09 +/- 0.09, GH vs. placebo, P = 0.07). Treatment with low-dose GH in obesity fails to alter fat mass despite a significant elevation in IGF-I and a shift in the global set point of E to F conversion consistent with inhibition of 11 beta-HSD1.
Tomlinson
Jeremy W
JW
Division of Medical Sciences, Queen Elizabeth Hospital, University of Birmingham, Birmingham, United Kingdom B15 2TH.
Crabtree
Nicola
N
Clark
Penny M S
PM
Holder
Geoff
G
Toogood
Andrew A
AA
Shackleton
Cedric H L
CH
Stewart
Paul M
PM
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D017667:Adipocytes / Q000187:drug effects*; D000273:Adipose Tissue / Q000201:enzymology; D001794:Blood Pressure / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003348:Cortisone / Q000097:blood; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D019382:Human Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008055:Lipids / Q000097:blood; D009765:Obesity / Q000188:drug therapy*; D010919:Placebos
D004791:Enzyme Inhibitors; D007328:Insulin; D008055:Lipids; D010919:Placebos; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D006913:Hydroxysteroid Dehydrogenases; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human; D003348:Cortisone; D006854:Hydrocortisone