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 Finken, M. J. J. Articles by Walker, B. R. Search for Related Content PubMed PubMed Citation Articles by Finken, M. J. J. Articles by Walker, B. R.

Cortisol Metabolism in Healthy Young Adults: Sexual Dimorphism in Activities of A-Ring Reductases, but not 11ß-Hydroxysteroid Dehydrogenases¹

University of Edinburgh, Endocrinology Unit, Department of Medical Sciences, Western General Hospital, Edinburgh, United Kingdom EH4 2XU

Address all correspondence and requests for reprints to: Dr. Brian R. Walker, University of Edinburgh, Endocrinology Unit, Department of Medical Sciences, Western General Hospital, Edinburgh, United Kingdom EH4 2XU. E-mail: b.walker{at}ed.ac.uk

Cortisol is metabolized irreversibly by A-ring reductases (5- and 5ß-reductases) and reversibly (to cortisone) by 11ß-hydroxysteroid dehydrogenases (11ßHSDs). In rats, estradiol down-regulates 11ßHSD1 expression. In humans, ratios of urinary cortisol/cortisone metabolites differ in men and women. In this study, urinary cortisol metabolites and hepatic 11ßHSD1 activity were measured in healthy young men and women at different phases of the menstrual cycle.

Ten men and 10 women with regular menstrual cycles collected a 24-h urine sample, took 250 µg oral dexamethasone at 2300 h, took 25 mg oral cortisone at 0900 h (after fasting), and had blood sampled for plasma cortisol estimation over the subsequent 150 min. Women repeated the tests in random order in menstrual, follicular, and luteal phases.

Women excreted disproportionately less A-ring-reduced metabolites of cortisol [median 5-tetrahydrocortisol, 1811 (interquartile range, 1391–2300) µg/day in menstrual phase vs. 2723 (interquartile range, 2454–3154) in men (P = 0.01); 5ß-tetrahydrocortisol, 1600 (interquartile range, 1419–1968) vs. 2197 (interquartile range, 1748–2995; P = 0.03)] but similar amounts of cortisol, cortisone, and tetrahydrocortisone. Analogous differences were observed in urinary excretion of androgen metabolites. Conversion of cortisone to cortisol on hepatic first pass metabolism was not different (peak plasma cortisol, 733 ± 60 nmol/L in women vs. 684 ± 53 nmol/L in men; mean ± SEM; P = 0.55). There were no differences in cortisol or androgen metabolism between phases of the menstrual cycle.

We conclude that sexual dimorphism in cortisol metabolite excretion is attributable to less A-ring reduction of cortisol in women, rather than less reactivation of cortisone to cortisol by 11ßHSD1. This difference is not influenced acutely by gonadal steroids. 11ßHSD1 has been suggested to modulate insulin sensitivity and body fat distribution, but caution must be exercised in extrapolating inferences about its regulation from rodents to man. A-Ring reductases may have an equally important influence on metabolic clearance of cortisol and intracellular cortisol concentrations.

This article has been cited by other articles:

				J. W. Tomlinson, J. Finney, C. Gay, B. A. Hughes, S. V. Hughes, and P. M. Stewart Impaired Glucose Tolerance and Insulin Resistance Are Associated With Increased Adipose 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Expression and Elevated Hepatic 5{alpha}-Reductase Activity Diabetes, October 1, 2008; 57(10): 2652 - 2660. [Abstract] [Full Text] [PDF]

				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]

				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]

				N van Montfoort, M J J Finken, S le Cessie, F W Dekker, and J M Wit Could cortisol explain the association between birth weight and cardiovascular disease in later life? A meta-analysis Eur. J. Endocrinol., December 1, 2005; 153(6): 811 - 817. [Abstract] [Full Text] [PDF]

				R. M Reynolds, B. R Walker, H. E Syddall, R. Andrew, P. J Wood, and D. I W Phillips Is there a gender difference in the associations of birthweight and adult hypothalamic-pituitary-adrenal axis activity? Eur. J. Endocrinol., February 1, 2005; 152(2): 249 - 253. [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]

				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]

				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]

				J Rovensky, R Imrich, J Koska, M Kovalancik, Z Killinger, J Payer, M Vigas, and D Jezova Cortisol elimination from plasma in premenopausal women with rheumatoid arthritis Ann Rheum Dis, July 1, 2003; 62(7): 674 - 676. [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]

				J. W. Tomlinson, N. Draper, J. Mackie, A. P. Johnson, G. Holder, P. Wood, and P. M. Stewart Absence of Cushingoid Phenotype in a Patient with Cushing's Disease due to Defective Cortisone to Cortisol Conversion J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 57 - 62. [Abstract] [Full Text] [PDF]

				R. Andrew, K. Smith, G. C. Jones, and B. R. Walker Distinguishing the Activities of 11{beta}-Hydroxysteroid Dehydrogenases in Vivo Using Isotopically Labeled Cortisol J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 277 - 285. [Abstract] [Full Text] [PDF]

				N. S. Stachenfeld, A. E. Splenser, W. L. Calzone, M. P. Taylor, and D. L. Keefe Genome and Hormones: Gender Differences in Physiology: Selected Contribution: Sex differences in osmotic regulation of AVP and renal sodium handling J Appl Physiol, October 1, 2001; 91(4): 1893 - 1901. [Abstract] [Full Text] [PDF]

				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]