Abstract |
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.
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Authors | Jeremy W Tomlinson, Nicola Crabtree, Penny M S Clark, Geoff Holder, Andrew A Toogood, Cedric H L Shackleton, Paul M Stewart |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 88
Issue 5
Pg. 2113-8
(May 2003)
ISSN: 0021-972X [Print] United States |
PMID | 12727963
(Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Inhibitors
- Insulin
- Lipids
- Placebos
- Human Growth Hormone
- Insulin-Like Growth Factor I
- Hydroxysteroid Dehydrogenases
- 11-beta-Hydroxysteroid Dehydrogenase Type 2
- HSD11B2 protein, human
- Cortisone
- Hydrocortisone
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Topics |
- 11-beta-Hydroxysteroid Dehydrogenase Type 2
- Adipocytes
(drug effects)
- Adipose Tissue
(enzymology)
- Blood Pressure
(drug effects)
- Body Composition
(drug effects)
- Cell Differentiation
(drug effects)
- Cell Division
(drug effects)
- Cortisone
(blood)
- Double-Blind Method
- Enzyme Inhibitors
(administration & dosage)
- Human Growth Hormone
(administration & dosage)
- Humans
- Hydrocortisone
(blood)
- Hydroxysteroid Dehydrogenases
(antagonists & inhibitors)
- Insulin
(blood)
- Insulin-Like Growth Factor I
(analysis)
- Lipids
(blood)
- Obesity
(drug therapy)
- Placebos
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