| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Rapid Communications |
University of Edinburgh (R.A., B.R.W.), Department of Medicine, Western General Hospital, Edinburgh, EH4 2XU, UK and MRC Environmental Epidemiology Unit (D.I.W.P.), Southampton General Hospital, Southampton S016 6YD, UK
Address correspondence to: Brian R. Walker, Department of Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland EH4 2XU.
Abstract
In obesity, urinary cortisol excretion is enhanced but plasma cortisol levels are elevated, suggesting that metabolic clearance of cortisol is increased. Cortisol is metabolised in liver and fat by A-ring reductases but also regenerated from inactive cortisone in liver, fat, and skeletal muscle by 11ß-reductase. These enzymes are regulated by estrogen. This study addressed whether there are differences in cortisol metabolism in obesity, and whether these differences are estrogen dependent.
31 men and 37 post-menopausal women (9 on estrogen replacement therapy)
aged 47–53 y supplied 24 h urine for gas chromatograph/mass
spectrometry. Total cortisol metabolite excretion was higher in men
than women, but weakly related to indices of obesity. By contrast,
metabolism of cortisol favoured 5
- rather than 5ß-reduction in
obese men and obese women, and favoured cortisol rather than cortisone
in obese men. In women compared with men ratio sof 5-/5ß-reduced
and cortisol/cortisone metabolites were also higher but these variables
were not affected by estrogen replacement therapy.
We conclude that in obesity, inactivation of cortisol by 5-reductase
is enhanced but this is offset by impaired metabolism of cortisol by
5ß-reductase in women and enhanced conversion of cortisone to
cortisol by 11ß-reductase in men. These observations suggest that
cortisol clearance is altered in obesity, and this may account for
activation of the hypothalamic-pituitary-adrenal axis. Moreover, these
data predict that obese subjects will have higher concentrations of
cortisol in key target tissues including liver and visceral fat. This
may contribute to the adverse metabolic consequences of obesity.
Received February 11, 1998.
This article has been cited by other articles:
 |
|
 |
|
  J. W. Tomlinson, J. Finney, B. A. Hughes, S. V. Hughes, and P. M. Stewart Reduced Glucocorticoid Production Rate, Decreased 5{alpha}-Reductase Activity, and Adipose Tissue Insulin Sensitization After Weight Loss Diabetes, June 1, 2008; 57(6): 1536 - 1543. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Roberge, A. C. Carpentier, M.-F. Langlois, J.-P. Baillargeon, J.-L. Ardilouze, P. Maheux, and N. Gallo-Payet Adrenocortical dysregulation as a major player in insulin resistance and onset of obesity Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1465 - E1478. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. Stimson, A. M. Johnstone, N. Z. M. Homer, D. J. Wake, N. M. Morton, R. Andrew, G. E. Lobley, and B. R. Walker Dietary Macronutrient Content Alters Cortisol Metabolism Independently of Body Weight Changes in Obese Men J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4480 - 4484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Kajantie, K. Feldt, K. Raikkonen, D. I. W. Phillips, C. Osmond, K. Heinonen, A.-K. Pesonen, S. Andersson, D. J. P. Barker, and J. G. Eriksson Body Size at Birth Predicts Hypothalamic-Pituitary-Adrenal Axis Response to Psychosocial Stress at Age 60 to 70 Years J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4094 - 4100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Barat, D. E. W. Livingstone, C. M. C. Elferink, C. R. McDonnell, B. R. Walker, and R. Andrew Effects of Gonadectomy on Glucocorticoid Metabolism in Obese Zucker Rats Endocrinology, October 1, 2007; 148(10): 4836 - 4843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Wudy, M. F. Hartmann, and T. Remer Sexual dimorphism in cortisol secretion starts after age 10 in healthy children: urinary cortisol metabolite excretion rates during growth Am J Physiol Endocrinol Metab, October 1, 2007; 293(4): E970 - E976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Berthiaume, M. Laplante, W. T. Festuccia, K. Cianflone, L. P. Turcotte, D. R. Joanisse, G. Olivecrona, R. Thieringer, and Y. Deshaies 11beta-HSD1 inhibition improves triglyceridemia through reduced liver VLDL secretion and partitions lipids toward oxidative tissues Am J Physiol Endocrinol Metab, October 1, 2007; 293(4): E1045 - E1052. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
F. Dadoun, P. Darmon, V. Achard, S. Boullu-Ciocca, F. Philip-Joet, M. C. Alessi, M. Rey, M. Grino, and A. Dutour Effect of sleep apnea syndrome on the circadian profile of cortisol in obese men Am J Physiol Endocrinol Metab, August 1, 2007; 293(2): E466 - E474. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Manco, J. M. Fernandez-Real, M. E. Valera-Mora, H. Dechaud, G. Nanni, V. Tondolo, M. Calvani, M. Castagneto, M. Pugeat, and G. Mingrone Massive Weight Loss Decreases Corticosteroid-Binding Globulin Levels and Increases Free Cortisol in Healthy Obese Patients: An adaptive phenomenon? Diabetes Care, June 1, 2007; 30(6): 1494 - 1500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D S Gardner, B W M Van Bon, J Dandrea, P J Goddard, S F May, V Wilson, T Stephenson, and M E Symonds Effect of periconceptional undernutrition and gender on hypothalamic-pituitary-adrenal axis function in young adult sheep. J. Endocrinol., August 1, 2006; 190(2): 203 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gambineri, V. Vicennati, S. Genghini, F. Tomassoni, U. Pagotto, R. Pasquali, and B. R. Walker Genetic Variation in 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Predicts Adrenal Hyperandrogenism among Lean Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2295 - 2302. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
L. M. Watts, V. P. Manchem, T. A. Leedom, A. L. Rivard, R. A. McKay, D. Bao, T. Neroladakis, B. P. Monia, D. M. Bodenmiller, J. X.-C. Cao, et al. Reduction of Hepatic and Adipose Tissue Glucocorticoid Receptor Expression With Antisense Oligonucleotides Improves Hyperglycemia and Hyperlipidemia in Diabetic Rodents Without Causing Systemic Glucocorticoid Antagonism Diabetes, June 1, 2005; 54(6): 1846 - 1853. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. Sandeep, R. Andrew, N. Z.M. Homer, R. C. Andrews, K. Smith, and B. R. Walker Increased In Vivo Regeneration of Cortisol in Adipose Tissue in Human Obesity and Effects of the 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Inhibitor Carbenoxolone Diabetes, March 1, 2005; 54(3): 872 - 879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Boullu-Ciocca, A. Dutour, V. Guillaume, V. Achard, C. Oliver, and M. Grino Postnatal Diet-Induced Obesity in Rats Upregulates Systemic and Adipose Tissue Glucocorticoid Metabolism During Development and in Adulthood: Its Relationship With the Metabolic Syndrome Diabetes, January 1, 2005; 54(1): 197 - 203. [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]
|
|
|
|
 |
|
 C. M. Masi, E. M. Rickett, L. C. Hawkley, and J. T. Cacioppo Gender and ethnic differences in urinary stress hormones: the population-based Chicago Health, Aging, and Social Relations Study J Appl Physiol, September 1, 2004; 97(3): 941 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Basu, R. J. Singh, A. Basu, E. G. Chittilapilly, C. M. Johnson, G. Toffolo, C. Cobelli, and R. A. Rizza Splanchnic Cortisol Production Occurs in Humans: Evidence for Conversion of Cortisone to Cortisol Via the 11-{beta} Hydroxysteroid Dehydrogenase (11{beta}-HSD) Type 1 Pathway Diabetes, August 1, 2004; 53(8): 2051 - 2059. [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]
|
|
|
|
 |
|
 K. J. McInnes, C. J. Kenyon, K. E. Chapman, D. E. W. Livingstone, L. J. Macdonald, B. R. Walker, and R. Andrew 5{alpha}-Reduced Glucocorticoids, Novel Endogenous Activators of the Glucocorticoid Receptor J. Biol. Chem., May 28, 2004; 279(22): 22908 - 22912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Q. Purnell, D. D. Brandon, L. M. Isabelle, D. L. Loriaux, and M. H. Samuels Association of 24-Hour Cortisol Production Rates, Cortisol-Binding Globulin, and Plasma-Free Cortisol Levels with Body Composition, Leptin Levels, and Aging in Adult Men and Women J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 281 - 287. [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]
|
|
|
|
|
|
T. Tsilchorozidou, J. W. Honour, and G. S. Conway Altered Cortisol Metabolism in Polycystic Ovary Syndrome: Insulin Enhances 5{alpha}-Reduction But Not the Elevated Adrenal Steroid Production Rates J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5907 - 5913. [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]
|
|
|
|
|
|
K. Herrick, D. I. W. Phillips, S. Haselden, A. W. Shiell, M. Campbell-Brown, and K. M. Godfrey Maternal Consumption of a High-Meat, Low-Carbohydrate Diet in Late Pregnancy: Relation to Adult Cortisol Concentrations in the Offspring J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3554 - 3560. [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]
|
|
|
|
|
|
D. Tiosano, I. Eisentein, D. Militianu, G. P. Chrousos, and Z.'e. Hochberg 11{beta}-Hydroxysteroid Dehydrogenase Activity in Hypothalamic Obesity J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 379 - 384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Andrews, O. Herlihy, D. E. W. Livingstone, R. Andrew, and B. R. Walker Abnormal Cortisol Metabolism and Tissue Sensitivity to Cortisol in Patients with Glucose Intolerance J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5587 - 5593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E.J. Brunner, H. Hemingway, B.R. Walker, M. Page, P. Clarke, M. Juneja, M.J. Shipley, M. Kumari, R. Andrew, J.R. Seckl, et al. Adrenocortical, Autonomic, and Inflammatory Causes of the Metabolic Syndrome: Nested Case-Control Study Circulation, November 19, 2002; 106(21): 2659 - 2665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Draper, S. M. Echwald, G. G. Lavery, E. A. Walker, R. Fraser, E. Davies, T. I. A. Sorensen, A. Astrup, J. Adamski, M. Hewison, et al. Association Studies between Microsatellite Markers within the Gene Encoding Human 11{beta}-Hydroxysteroid Dehydrogenase Type 1 and Body Mass Index, Waist to Hip Ratio, and Glucocorticoid Metabolism J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 4984 - 4990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Rask, B. R. Walker, S. Soderberg, D. E. W. Livingstone, M. Eliasson, O. Johnson, R. Andrew, and T. Olsson Tissue-Specific Changes in Peripheral Cortisol Metabolism in Obese Women: Increased Adipose 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Activity J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3330 - 3336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Masuzaki, J. Paterson, H. Shinyama, N. M. Morton, J. J. Mullins, J. R. Seckl, and J. S. Flier A Transgenic Model of Visceral Obesity and the Metabolic Syndrome Science, December 7, 2001; 294(5549): 2166 - 2170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Jessop, M. F. Dallman, D. Fleming, and S. L. Lightman Resistance to Glucocorticoid Feedback in Obesity J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4109 - 4114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Johansson, R. Andrew, H. Forsberg, K. Cederquist, B. R. Walker, and T. Olsson Glucocorticoid Metabolism and Adrenocortical Reactivity to ACTH in Myotonic Dystrophy J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4276 - 4283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. B. Whorwood, S. J. Donovan, P. J. Wood, and D. I. W. Phillips Regulation of Glucocorticoid Receptor {{alpha}} and {beta} Isoforms and Type I 11{beta}-Hydroxysteroid Dehydrogenase Expression in Human Skeletal Muscle Cells: A Key Role in the Pathogenesis of Insulin Resistance? J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2296 - 2308. [Abstract] [Full Text]
|
|
|
|
|
|
R. M. Reynolds, B. R. Walker, H. E. Syddall, R. Andrew, P. J. Wood, C. B. Whorwood, and D. I. W. Phillips Altered Control of Cortisol Secretion in Adult Men with Low Birth Weight and Cardiovascular Risk Factors J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 245 - 250. [Abstract] [Full Text]
|
|
|
|
|
|
N. S. Levitt, E. V. Lambert, D. Woods, C. N. Hales, R. Andrew, and J. R. Seckl Impaired Glucose Tolerance and Elevated Blood Pressure in Low Birth Weight, Nonobese, Young South African Adults: Early Programming of Cortisol Axis J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4611 - 4618. [Abstract] [Full Text]
|
|
|
|
|
|
P. Ferrari Author's Response: In Vivo Measurements of Renal 11{beta}-Hydroxysteroid Dehydrogenase Type 2 Activity J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4922 - 4923. [Full Text]
|
|
|
|
|
|
M. Quinkler, W. Oelkers, and S. Diederich In Vivo Measurement of Renal 11{beta}-Hydroxysteroid Dehydrogenase Type 2 Activity J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4921a - 4922. [Full Text]
|
|
|
|
|
|
V. Vicennati and R. Pasquali Abnormalities of the Hypothalamic-Pituitary-Adrenal Axis in Nondepressed Women with Abdominal Obesity and Relations with Insulin Resistance: Evidence for a Central and a Peripheral Alteration J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4093 - 4098. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Stokes, J. Noble, L. Brett, C. Phillips, J. R. Seckl, C. O’Brien, and R. Andrew Distribution of Glucocorticoid and Mineralocorticoid Receptors and 11{beta}-Hydroxysteroid Dehydrogenases in Human and Rat Ocular Tissues Invest. Ophthalmol. Vis. Sci., June 1, 2000; 41(7): 1629 - 1638. [Abstract] [Full Text]
|
|
|
|
|
|
A. A. Toogood, N. F. Taylor, S. M. Shalet, and J. P. Monson Modulation of Cortisol Metabolism by Low-Dose Growth Hormone Replacement in Elderly Hypopituitary Patients J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1727 - 1730. [Abstract] [Full Text]
|
|
|
|
|
|
D. E. W. Livingstone, G. C. Jones, K. Smith, P. M. Jamieson, R. Andrew, C. J. Kenyon, and B. R. Walker Understanding the Role of Glucocorticoids in Obesity: Tissue-Specific Alterations of Corticosterone Metabolism in Obese Zucker Rats Endocrinology, February 1, 2000; 141(2): 560 - 563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jamieson, A. M. Wallace, R. Andrew, B. S. Nunez, B. R. Walker, R. Fraser, P. C. White, and J. M. C. Connell Apparent Cortisone Reductase Deficiency: A Functional Defect in 11{beta}-Hydroxysteroid Dehydrogenase Type 1 J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3570 - 3574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. J. Finken, R. C. Andrews, R. Andrew, and B. R. Walker Cortisol Metabolism in Healthy Young Adults: Sexual Dimorphism in Activities of A-Ring Reductases, but not 11{beta}-Hydroxysteroid Dehydrogenases J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3316 - 3321. [Abstract] [Full Text]
|
|
|
|
|
|
B. E. P. Murphy Lack of Specificity of Urinary Free Cortisol Determinations: Why Does It Continue? J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2258a - 2259. [Full Text]
|
|
|
|
 |
|
 R. Fraser, M. C. Ingram, N. H. Anderson, C. Morrison, E. Davies, and J. M. C. Connell Cortisol Effects on Body Mass, Blood Pressure, and Cholesterol in the General Population Hypertension, June 1, 1999; 33(6): 1364 - 1368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Stewart, A. Boulton, S. Kumar, P. M. S. Clark, and C. H. L. Shackleton Cortisol Metabolism in Human Obesity: Impaired Cortisone->Cortisol Conversion in Subjects with Central Adiposity J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 1022 - 1027. [Abstract] [Full Text]
|
|
|
|
|
|
N. M. Morton, M. C. Holmes, C. Fievet, B. Staels, A. Tailleux, J. J. Mullins, and J. R. Seckl Improved Lipid and Lipoprotein Profile, Hepatic Insulin Sensitivity, and Glucose Tolerance in 11beta -Hydroxysteroid Dehydrogenase Type 1 Null Mice J. Biol. Chem., October 26, 2001; 276(44): 41293 - 41300. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
