We have demonstrated 11 beta-HSD oxo-reductase activity in subcutaneous abdominal adipose tissue, which may be increased in obesity.

OBJECTIVE: We examined the relationship of adiposity to pituitary ± adrenal responses to corticotrophin-releasing hormone (CRH) in men and postmenopausal women, controlling for the in¯uence of depression. DESIGN: Studies of CRH responses, cortisol metabolite levels and depression scores in relation to adiposity in men and postmenopausal women. SUBJECTS: Thirteen men: age (median, interquartile range) 62 y (52 ± 63), body mass index (BMI) 29.0 kgam 2 (26.3 ± 33.1), waist circumference (waist) 105 cm (97 ± 111), waist : hip ratio (WHR) 1.03 (0.98 ± 1.07), subscapular to triceps skinfold thickness ratio (STR) 2.0 (1.2 ± 2.4), total body fat (TBF) 25.4 kg (19.8 ± 28.8); and eight women: age 54 y (53 ± 62), BMI 30 kgam 2 (23 ± 41), waist 86 cm (79 ± 117), WHR 0.94 (0.87 ± 1.10), STR 1.0 (0.85 ± 1.07), TBF 35.0 kg (18.7 ± 48.8). MEASUREMENTS: A standard CRH test was conducted with additional basal samples taken for leptin and interleukin 6 (IL-6). Total urine cortisol metabolites (TCM) and the ratio of urinary cortisol : cortisone (FmaEm) metabolites were measured. Depression scores were measured by the General Health Questionnaire (GHQ-30) and Hospital Anxiety and Depression Scale (HAD) questionnaire. All subjects completed an overnight dexamethasone suppression test. RESULTS: The basal to peak percentage increments (%inc.) in adrenocorticotrophic hormone (ACTH) and cortisol in men correlated directly with STR (ACTH %inc. r 0.70, P`0.01; cortisol %inc. r 0.55, P 0.05); this relationship was independent of depression scores. In women, the ACTH area under incremental curve (AUIC) correlated negatively with STR (r À0.81, P`0.05). In men, but not in women, there was a signi®cant correlation between GHQ-30 score and ACTH AUIC (r 0.62, P`0.05) and cortisol AUIC (r 0.72, P`0.01). Depression scores were consistently and directly related to indices of obesity and central obesity. There were no signi®cant relationships in either sex between urinary TCM or FmaEm ratio and BMI, waist, WHR, TBF, STR or CRH responses. The urinary FmaEm ratio was higher in men than in women (median 0.74 vs 0.66, P`0.05). In men, but not in women, GHQ-30 scores correlated positively with urinary TCM (r 0.57, P 0.05) and HAD-depression scores were inversely related to the urine FmaEm ratio (r À0.65, P`0.05). All subjects suppressed normally with dexamethasone. CONCLUSIONS: Cortisol metabolite levels were increased in depression in men, but were not related to adiposity in either sex. We demonstrate that central obesity in men, but not postmenopausal women, is associated with an enhanced pituitary ± adrenal response to CRH and that this relationship is independent of depression score.

Objectives: To determine the dependence of plasma leptin concentrations upon circulating noradrenaline (NA) and thyroid hormones (TH) in humans. Design: Cross-sectional study in 40 newly diagnosed untreated patients with primary thyroid disease, and 69 lean and obese euthyroid control subjects. Measurements: Plasma leptin, NA, free T3 (fT3) and TSH in the fasting state. Anthropometry and % body fat (electrical bioimpedance). Results: Leptin levels were highest in 37 obese euthyroid and 22 hypothyroid (median [interquartiles]31.5 [19.0 ± 48.0], 19.2 [11.5 ± 31.5] ng ml 71 ), and lowest in 32 lean euthyroid and 18 hyperthyroid subjects (6.6 [3.9 ± 14.4], 8.9 [5.5 ± 11.1]; ANOVA, P`0.0001). Plasma NA was similar in all groups (P n.s.). In obese controls, TSH correlated with % body fat and leptin (r 0.67, r 0.61; P`0.001). Treatment of hypothyroidism (n 10) with T4 reduced leptin from 20. 8 [11.8 ± 31.6] to 12.9 [4.6 ± 21.2] (P 0.005) with no change in BMI. Conclusions: Thyroid status modi®es leptin secretion independently of adiposity and NA. The data suggest leptin ± thyroid interactions at hypothalamic and adipocyte level.

There is evidence for enhanced hypothalamo ± pituitary ± adrenal axis (HPAA) activity in centrally obese premenopausal women. This has led to the hypothesis that increased cortisol production rates may be an aetiological factor in the genesis of central obesity. However, the relationship of obesity and body fat distribution to HPAA activity in men and postmenopausal women has not been established. We carried out CRH tests in 13 men and 8 post-menopausal women. We measured 24 h urine cortisol metabolites prior to the CRH test in each subject, as an indication of cortisol production rate. There was a signi®cant direct relationship between central obesity as measured by the ratio of subscapular : triceps skinfold thickness (STR) Ð and the ACTHacortisol response to CRH in men, but not in postmenopausal women. There was no relationship between obesity or body fat distribution and 24 h urine cortisol metabolites. This study provides evidence for hyperactivity of the HPAA in centrally obese men, but not in postmenopausal women.