This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tomlinson, J. W. Articles by Stewart, P. M. Search for Related Content PubMed PubMed Citation Articles by Tomlinson, J. W. Articles by Stewart, P. M.

Low-Dose Growth Hormone Inhibits 11ß-Hydroxysteroid Dehydrogenase Type 1 but Has No Effect upon Fat Mass in Patients with Simple Obesity

Division of Medical Sciences (J.W.T., A.A.T., P.M.S.) and Department of Nuclear Medicine (N.C.), Queen Elizabeth Hospital, University of Birmingham, Birmingham, United Kingdom B15 2TH; Regional Endocrine Laboratory (P.M.S.C., G.H.), Department of Clinical Biochemistry, University Hospital Birmingham NHS Trust, Birmingham, United Kingdom B29 6JD; and Children’s Hospital (C.H.L.S.), Oakland Research Institute, Oakland, California 94609-1809

Address all correspondence and requests for reprints to: Prof. P. M. Stewart, M.D., F.R.C.P., F.Med.Sci., Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom B15 2TH. E-mail: p.m.stewart{at}bham.ac.uk.

GH has potent effects on adipocyte biology, stimulating lipolysis but also promoting preadipocyte proliferation. In addition, GH, acting through IGF-I, inhibits 11 ß-hydroxysteroid dehydrogenase type 1 (11ß-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 11ß-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 11ß-HSD1.

This work was supported in part by a research grant from Pharmacia and Upjohn. P.M.S. is a Medical Research Council (MRC) Senior Fellow, and J.W.T. is a MRC clinical training fellow.

Abbreviations: 11ß-HSD1, 11ß-Hydroxysteroid dehydrogenase type 1; BMI, body mass index; DEXA, dual-energy x-ray absorptiometry; E, cortisone; F, cortisol; GHD, GH deficiency; GR, glucocorticoid receptor; HDL, high-density lipoprotein; HOMA, homeostasis model assessment; THE, tetrahydrometabolites of E; THF + 5THF, tetrahydrometabolites of F; UFE, urinary free E; UFF, urinary free F.

This article has been cited by other articles:

				K. C. Mekala and N. A. Tritos Effects of Recombinant Human Growth Hormone Therapy in Obesity in Adults: A Metaanalysis J. Clin. Endocrinol. Metab., January 1, 2009; 94(1): 130 - 137. [Abstract] [Full Text] [PDF]

				S. D'Amico, J. Shi, R. V Sekhar, F. Jahoor, K. J Ellis, K. Rehman, J. Willis, M. Maldonado, and A. Balasubramanyam Physiologic growth hormone replacement improves fasting lipid kinetics in patients with HIV lipodystrophy syndrome Am. J. Clinical Nutrition, July 1, 2006; 84(1): 204 - 211. [Abstract] [Full Text] [PDF]

				S. K. Paulsen, S. B. Pedersen, J. O. L. Jorgensen, S. Fisker, J. S. Christiansen, A. Flyvbjerg, and B. Richelsen Growth Hormone (GH) Substitution in GH-Deficient Patients Inhibits 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Messenger Ribonucleic Acid Expression in Adipose Tissue J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1093 - 1098. [Abstract] [Full Text] [PDF]

				H. A Sigurjonsdottir, J. Koranyi, M. Axelson, B.-A. Bengtsson, and G. Johannsson GH effect on enzyme activity of 11{beta}HSD in abdominal obesity is dependent on treatment duration Eur. J. Endocrinol., January 1, 2006; 154(1): 69 - 74. [Abstract] [Full Text] [PDF]

				M. Quinkler, D. Zehnder, J. Lepenies, M. D Petrelli, J. S Moore, S. V Hughes, P. Cockwell, M. Hewison, and P. M Stewart Expression of renal 11{beta}-hydroxysteroid dehydrogenase type 2 is decreased in patients with impaired renal function Eur. J. Endocrinol., August 1, 2005; 153(2): 291 - 299. [Abstract] [Full Text] [PDF]

				N. Draper and P. M Stewart 11{beta}-Hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action J. Endocrinol., August 1, 2005; 186(2): 251 - 271. [Abstract] [Full Text] [PDF]

				J. W. Tomlinson, E. A. Walker, I. J. Bujalska, N. Draper, G. G. Lavery, M. S. Cooper, M. Hewison, and P. M. Stewart 11{beta}-Hydroxysteroid Dehydrogenase Type 1: A Tissue-Specific Regulator of Glucocorticoid Response Endocr. Rev., October 1, 2004; 25(5): 831 - 866. [Abstract] [Full Text] [PDF]

				J. M. Harkins, N. Moustaid-Moussa, Y.-J. Chung, K. M. Penner, J. J. Pestka, C. M. North, and K. J. Claycombe Expression of Interleukin-6 Is Greater in Preadipocytes than in Adipocytes of 3T3-L1 Cells and C57BL/6J and ob/ob Mice J. Nutr., October 1, 2004; 134(10): 2673 - 2677. [Abstract] [Full Text] [PDF]

				J. R. Seckl, N. M. Morton, K. E. Chapman, and B. R. Walker Glucocorticoids and 11beta-Hydroxysteroid Dehydrogenase in Adipose Tissue Recent Prog. Horm. Res., January 1, 2004; 59(1): 359 - 393. [Abstract] [Full Text]