SEXUAL DIMORPHISM IN 11BETA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITY ANDITS RELATION TO FAT DISTRIBUTION AND INSULIN SENSITIVITY - A STUDY INHYPOPITUITARY SUBJECTS

OBJECTIVE Sexual dimorphism of 11 P hydroxysteroid dehydrogenase activ ity (11 P HSD) as measured by the urinary 11-OH/11-oxo cortisol metabo lite ratio has been documented in healthy subjects. Since body composi tion, fat distribution and insulin sensitivity vary between the sexes we have investigated whether these factors may account for the observe d difference. Studies were performed in ACTH deficient hypopituitary s ubjects to eliminate the effect of feedback modulation of cortisol sec retion. DESIGN AND PATIENTS 44 hypopituitary patients, (m:f, 32:12), m edian age 51years, median weight 86kg, on hydrocortisone and other rep lacement therapy as appropriate were studied. MEASUREMENT Urine 11-OH/ 11-oxo cortisol metabolites and serum and urine cortisone (E) and cort isol (F) were measured in relation to total cortisol metabolites and c ortisol binding globulin; fat distribution was assessed by Dual Energy X-ray absorptiometry (DXA), and insulin sensitivity by homeostatic mo del of assessment. RESULTS Cortisol bioavailability (total urine corti sol metabolites, urine free cortisol and cortisol binding globulin) wa s similar in both sexes. The 11-OH/11-oxo ratio was lower in females t han males (median; 0.99 vs 1.3, P< 0.03) while thyroid status was simi lar. 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 lowe r 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 fa t, (P< 0.01) and directly correlated to insulin sensitivity, P< 0.01. Stepwise regression analysis showed gynoid fat to be the most importan t 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 (m edian; 1.0 vs 1.7, P<0.05). The urine and serum F and E and their rati o (FIE) were similar in these groups. CONCLUSION These data confirm th e presence of sexual dimorphism in 11 p-hydroxysteroid dehydrogenase a ctivity 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 d etermined by the activity of type 1 and not type 2 11 p-hydroxysteroid dehydrogenase.