Sexual dimorphism in 11 β hydroxysteroid dehydrogenase activity and its relation to fat distribution and insulin sensitivity;: a study in hypopituitary subjects

OBJECTIVE Sexual dimorphism of 11 P hydroxysteroid dehydrogenase activity (11 P HSD) as measured by the urinary 11-OH/11-oxo cortisol metabolite ratio has been documented in healthy subjects. Since body composition, fat distribution and insulin sensitivity vary between the sexes we have investigated whether these factors may account for the observed difference. Studies were performed in ACTH deficient hypopituitary subjects to eliminate the effect of feedback modulation of cortisol secretion. DESIGN AND PATIENTS 44 hypopituitary patients, (m:f, 32:12), median age 51years, median weight 86kg, on hydrocortisone and other replacement therapy as appropriate were studied. MEASUREMENT Urine 11-OH/11-oxo cortisol metabolites and serum and urine cortisone (E) and cortisol (F) were measured in relation to total cortisol metabolites and cortisol binding globulin; fat distribution was assessed by Dual Energy X-ray absorptiometry (DXA), and insulin sensitivity by homeostatic model of assessment. RESULTS Cortisol bioavailability (total urine cortisol metabolites, urine free cortisol and cortisol binding globulin) was similar in both sexes. The 11-OH/11-oxo ratio was lower in females than males (median; 0.99 vs 1.3, P< 0.03) while thyroid status was similar. Females had higher percentage fat (median 47.7 vs 34.9, P<0.01); total fat (median 39.5 vs 34.9 kg, P<0.01), android fat (median 9.1 vs 6.6 kg, P< 0.01); gynoid fat (median; 9.9 vs 6.8 kg, P<0.05) and lower insulin sensitivity (median 15.3 vs 30.6, P<0.01). In all subjects, the 11-OH/11- oxo ratio was inversely related to body weight (P<0.01), % fat (P<0.05), total fat (P< 0.01), android fat (P< 0.01), gynoid fat, (P< 0.01) and directly correlated to insulin sensitivity, P< 0.01. Stepwise regression analysis showed gynoid fat to be the most important factor determining the 11-OH/11-oxo ratio. In 24 subjects (f:m, 8:16) on exogenous sex steroid therapy insulin sensitivity was similar but the sexual dimorphism of the 11-OH/11-oxo ratio remained unchanged (median; 1.0 vs 1.7, P<0.05). The urine and serum F and E and their ratio (FIE) were similar in these groups. CONCLUSION These data confirm the presence of sexual dimorphism in 11 p-hydroxysteroid dehydrogenase activity in hypopituitary patients as described in normal individuals. This is the first in vivo evidence that this dimorphism is related to body composition. Our findings suggest that sexual dimorphism may be determined by the activity of type 1 and not type 2 11 p-hydroxysteroid dehydrogenase.