Production Rates of Cortisol in Obesity

Abstract

VIERHAPPER, HEINRICH, PETER NOWOTNY, AND WERNER WALDHÄ USL. Production rates of cortisol in obesity. Obes Res. 2004;12:1421-1425. Objective: To determine the metabolic clearance rates (MCRs) and endogenous production rates (PRs) of cortisol (F) in grades 2 and 3 obese men (n ϭ 9) and women (n ϭ 6). Research Methods and Procedures:The MCRs and the endogenous PRs of cortisol (F) were determined in grades 2 and 3 obese men (n ϭ 9) and women (n ϭ 6) using the stable isotope dilution technique and mass spectrometry. Results: In obese women, endogenous PRs of F (0.6 Ϯ 0.4 mg/h) were similar to those of nonobese women, but MCRs of F were higher in obese women (9 Ϯ 4 L/h) compared with nonobese women (5 ϩ 2 L/h; p Ͻ 0.05). The MCR of F was correlated with the ratio of excreted cortisone to F metabolites. Furthermore, obese women were characterized by an increased ratio of androsterone to etiocholanolone (p Ͻ 0.01). In obese men, the MCRs (11 Ϯ 6 L/h) and the endogenous PRs of F (0.6 Ϯ 0.3 mg/h) were both similar to those of nonobese men, but the MCR of F was directly correlated with the ratio of excreted cortisone to F metabolites (r ϭ 0.7833, p ϭ 0.012). Discussion: These data demonstrate sex-specific differences in F metabolism in obesity. The rise in MCRs of F is more pronounced in obese women than in men. However, the increase in the MCR of F is moderate in both genders and exceeds the normal range only in a subgroup of obese individuals.

Enhanced cortisol production rates, free cortisol, and 11β-HSD-1 expression correlate with visceral fat and insulin resistance in men: effect of weight loss

“…The mean (range) of MCR in all 24 men was 326 (133-570) l/day, which is in close agreement with previous studies (36,45).…”

Sex‐specific Difference in the Interconversion of Cortisol and Cortisone in Men and Women

“…Differences in the activity of 11β‐HSD1 between men and women were initially based on findings in men with hypopituitarism, i.e., in the absence of pituitary feedback mechanisms, and in elderly men (5, 6) who present, albeit with a substantial overlap between the members of the two sexes, a relative preponderance of urinary metabolites with an 11‐hydroxy group (metabolites of cortisol) over their 11‐keto homologues (metabolites of cortisone) as compared with women, suggesting a higher oxoreductase activity of 11β‐HSD1 in men. As demonstrated previously (17) and confirmed by the results of the present investigation, these differences are not apparent in young, non‐obese men and women with intact pituitary function who show an identical relationship of the urinary metabolites of cortisol and of cortisone. Hence, the determination of glucocorticoid metabolites in 24‐hour urine samples, which reflects the action of two different 11β‐hydroxysteroid dehydrogenases (11β‐HSD type 1 and type 2), and the variable activity of 11β‐HSD1 in different tissues are not precise enough to document sex‐specific differences in healthy individuals.…”

Brief review: Glucocorticoid excretion in obesity

“…However, this mechanism of parallel changes in metabolic clearance and adrenocortical activity has not been observed in all obese subjects [31]. In principle, metabolic cortisol clearance in liver and fat involves varying 11␤-oxidation, leading to reduced or increased conversion rates of cortisol to cortisone, and depends on A-ring reduction, resulting in formation of the irreversible 5␣-and 5␤-tetrahydrocortisol (THF) metabolites [32].…”