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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1999-10-6
pubmed:abstractText
Cortisol is metabolized irreversibly by A-ring reductases (5alpha- and 5beta-reductases) and reversibly (to cortisone) by 11beta-hydroxysteroid dehydrogenases (11betaHSDs). In rats, estradiol down-regulates 11betaHSD1 expression. In humans, ratios of urinary cortisol/cortisone metabolites differ in men and women. In this study, urinary cortisol metabolites and hepatic 11betaHSD1 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 microg 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 5alpha-tetrahydrocortisol, 1811 (interquartile range, 1391-2300) microg/day in menstrual phase vs. 2723 (interquartile range, 2454-3154) in men (P = 0.01); 5beta-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 11betaHSD1. This difference is not influenced acutely by gonadal steroids. 11BetaHSD1 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-972X
pubmed:author
pubmed:issnType
Print
pubmed:volume
84
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3316-21
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Cortisol metabolism in healthy young adults: sexual dimorphism in activities of A-ring reductases, but not 11beta-hydroxysteroid dehydrogenases.
pubmed:affiliation
University of Edinburgh, Department of Medical Sciences, Western General Hospital, United Kingdom.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't