Recent evidence suggests that endogenous glucocorticoids (GC) may be suppressed by adipocyte-derived leptin and elevated by dietary acidity. Therefore we examined whether these factors might be predictors of potentially bioactive free glucocorticoids independently of adrenocortical activity.
Body composition, plasma cortisol, plasma leptin, 24-h urinary excretion rates of net acid (NAE) reflecting daily diet-dependent acid load, total nitrogen, urinary free cortisol (UFF), free cortisone (UFE), the main GC metabolites tetrahydrocortisone (THE), tetrahydrocortisol (THF) and 5alpha-tetrahydrocortisol (alloTHF) were examined cross-sectionally in 30 healthy adults (15 females; 2244 yr old; BMI: 2025 kg/m). Adrenocortical activity (AA) was assessed by the sum of the 3 major glucocorticoid metabolites (THE+THF+alloTHF), reflecting overall daily cortisol secretion. As a measure of potentially bioactive free GCs (bioactiveGCs) the sum of free cortisol and cortisone in urine (UFF+UFE) was taken, reflecting the free fraction of circulating cortisol and cortisone.
Plasma leptin (mean±SD, 2.8±1.6 vs. 7.6±4.9 ng/mL) and percent body fat (%BF, 16.8±4.2 vs. 26.9±4.9%) were lower (P<0.01) and body surface (BS)-corrected AA higher (P<0.01) in males, whereas plasma cortisol and BS-corrected bioactiveGCs were statistically undistinguishable between the sexes. Both bioactiveGCs and AA correlated positively with %BF and leptin in males (P<0.05), but not in females. After adjusting for AA, NAE was a positive (P=0.011) and leptin a negative (P=0.046) predictor of bioactiveGCs in females (total explained variability R2=0.71). In males only AA explained variation of bioactive-GCs (R2=0.49, P=0.004).
Our findings indicate that at least in females variability of potentially bioactive glucocorticoids is not only explained by individual adreno-cortical activity, but may also be affected by circulating leptin and diet-dependent daily acid load.