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 Tiosano, D. Articles by Hochberg, Z.'e. Search for Related Content PubMed PubMed Citation Articles by Tiosano, D. Articles by Hochberg, Z.'e. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB HYDROCORTISONE Medline Plus Health Information Obesity Obesity in Children

11ß-Hydroxysteroid Dehydrogenase Activity in Hypothalamic Obesity

Departments of Pediatrics (D.T., I.E., Z.H.) and Radiology (D.M.), Meyer Children’s Hospital, Haifa 31096, Israel; and National Institute of Child Health and Human Development, Pediatric and Reproductive Endocrinology Branch (G.P.C., Z.H.), Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Ze’ev Hochberg, M.D., D.Sc., Meyer Children’s Hospital, P.O. Box 9602, Haifa 31096, Israel. E-mail: z_hochberg{at}rambam.health.gov.il.

After extensive suprasellar operations for hypothalamic tumor removal, some patients develop Cushing-like morbid obesity while they receive replacement doses of glucocorticoids. In this study, we examined the hypothesis that target tissue conversion of inactive 11-ketosteroids to active 11ß-OH glucocorticoids might explain the obesity of some patients with hypothalamic lesions. Toward this aim, we studied 10 patients with hypothalamic obesity and secondary adrenal insufficiency and 6 control Addisonian patients while they were on glucocorticoid replacement therapy. Pituitary hormone deficiencies were replaced when medically indicated. Twenty-four-hour urine was collected after a single oral dose of 12 mg/m² hydrocortisone acetate. The ratios of free and conjugated cortisol (F) to cortisone (E) and their metabolites, [tetrahydrocortisol (THF)+5THF]/tetrahyrdocortisone (THE), dihydrocortisols/dihydrocortisones, cortols/cortolones, and (F+E)/(THF+THE+5THF), were considered to represent 11ß-hydroxysteroid dehydrogenase (HSD) activity. The 11-OH/11-oxo ratios were significantly higher in the urine of patients with hypothalamic obesity. The 11-OH/11-oxo ratios, however, did not correlate with the degree of obesity, yet a significant correlation was found between conjugated F/E and the ratio of visceral fat to sc fat measured by computerized tomography at the umbilical level. The consequence of increased 11ß-HSD1 activity and the shift of the interconversion toward cortisol may contribute to the effects of the latter in adipose tissue. We propose that deficiency of hypothalamic messengers after surgical injury induces a paracrine/autocrine effect of enhanced glucocorticoid activity due to up-regulated 11ß-HSD1 activity.

Abbreviations: BMI, Body mass index; CT, computerized tomography; E, cortisone; F, cortisol; HSD, hydroxysteroid dehydrogenase; THE, tetrahydrocortisone; THF, tetrahydrocortisol.

This article has been cited by other articles:

				S. Wiegand, A. Richardt, T. Remer, S. A Wudy, J. W Tomlinson, B. Hughes, A. Gruters, P. M Stewart, C. J Strasburger, and M. Quinkler Reduced 11{beta}-hydroxysteroid dehydrogenase type 1 activity in obese boys Eur. J. Endocrinol., September 1, 2007; 157(3): 319 - 324. [Abstract] [Full Text] [PDF]

				R. Basu, R. J. Singh, A. Basu, E. G. Chittilapilly, M. C. Johnson, G. Toffolo, C. Cobelli, and R. A. Rizza Obesity and Type 2 Diabetes Do Not Alter Splanchnic Cortisol Production in Humans J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 3919 - 3926. [Abstract] [Full Text] [PDF]

				O. Fruchter, T. Kino, E. Zoumakis, S. Alesci, M. De Martino, G. Chrousos, and Z. Hochberg The Human Glucocorticoid Receptor (GR) Isoform {beta} Differentially Suppresses GR{alpha}-Induced Transactivation Stimulated by Synthetic Glucocorticoids J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3505 - 3509. [Abstract] [Full Text] [PDF]

				P. W. Speiser, M. C. J. Rudolf, H. Anhalt, C. Camacho-Hubner, F. Chiarelli, A. Eliakim, M. Freemark, A. Gruters, E. Hershkovitz, L. Iughetti, et al. Childhood Obesity J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1871 - 1887. [Abstract] [Full Text] [PDF]

				Y. Liu, Y. Nakagawa, Y. Wang, R. Sakurai, P. V. Tripathi, K. Lutfy, and T. C. Friedman Increased Glucocorticoid Receptor and 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Expression in Hepatocytes May Contribute to the Phenotype of Type 2 Diabetes in db/db Mice Diabetes, January 1, 2005; 54(1): 32 - 40. [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. W. Tomlinson, J. S. Moore, P. M. S. Clark, G. Holder, L. Shakespeare, and P. M. Stewart Weight Loss Increases 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Expression in Human Adipose Tissue J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2711 - 2716. [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]

				H. Mersebach, O. L. Svendsen, A. Astrup, and U. Feldt-Rasmussen Abnormal Sympathoadrenal Activity, but Normal Energy Expenditure in Hypopituitarism J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5689 - 5695. [Abstract] [Full Text] [PDF]

				J. Westerbacka, H. Yki-Jarvinen, S. Vehkavaara, A.-M. Hakkinen, R. Andrew, D. J. Wake, J. R. Seckl, and B. R. Walker Body Fat Distribution and Cortisol Metabolism in Healthy Men: Enhanced 5{beta}-Reductase and Lower Cortisol/Cortisone Metabolite Ratios in Men with Fatty Liver J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4924 - 4931. [Abstract] [Full Text] [PDF]

				D. J. Wake, E. Rask, D. E. W. Livingstone, S. Soderberg, T. Olsson, and B. R. Walker Local and Systemic Impact of Transcriptional Up-Regulation of 11{beta}-Hydroxysteroid Dehydrogenase Type 1 in Adipose Tissue in Human Obesity J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3983 - 3988. [Abstract] [Full Text] [PDF]

				R. S. Lindsay, D. J. Wake, S. Nair, J. Bunt, D. E. W. Livingstone, P. A. Permana, P. A. Tataranni, and B. R. Walker Subcutaneous Adipose 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Activity and Messenger Ribonucleic Acid Levels Are Associated with Adiposity and Insulinemia in Pima Indians and Caucasians J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2738 - 2744. [Abstract] [Full Text] [PDF]

				B. R. Walker and R. Andrew Cortisol Metabolism in Type 2 Diabetes J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2951 - 2952. [Full Text] [PDF]

				M. Friedberg, E. Zoumakis, N. Hiroi, T. Bader, G. P. Chrousos, and Z.'e. Hochberg Modulation of 11{beta}-Hydroxysteroid Dehydrogenase Type 1 in Mature Human Subcutaneous Adipocytes by Hypothalamic Messengers J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 385 - 393. [Abstract] [Full Text] [PDF]