Interdependence of the peripheral metabolism of glucocorticoids and thyroid hormones under calorie deficit in rats at different ages

The joint effects of energy restriction and age on adrenal glucocorticoid synthesis, liver signalling and liver thyroid hormone metabolism were examined. Adrenal type 1 11β-hydroxylase expression was chosen as a marker of adrenal steroidogenesis, liver 11β-hydroxysteroid dehydrogenase 1 and glucocorticoid receptor proteins as measures of glucocorticoid signalling, and liver type 1 and 3 deiodinase proteins as determinants of thyroid hormone metabolism. A nine-week study covered two groups (n = 21 each) of 17- and 45-week-old Sprague-Dawley male rats fed ad libitum and on diets with 20% or 40% energy deficit. Adrenal type 1 11β-hydroxylase mRNA and protein, hepatic type 1 11β-hydroxysteroid dehydrogenase level, glucocorticoid receptor and type 1 and 3 deiodinase protein levels, as well as plasma adrenocorticotropic hormone (ACTH) and corticosterone concentrations. Calorie restriction increased ACTH plasma concentrations and type 1 11β-hydroxylase protein levels were determined. Plasma ACTH and type 1 11β-hydroxylase protein were higher in older rats, while in the younger group, type 1 deiodinase protein exceeded the enzyme level in older rats. Calorie restriction decreased plasma corticosterone and type 1 11β-hydroxysteroid dehydrogenase only in older rats. Direct relationships between glucocorticoid receptors and type 1 and 3 deiodinases, as well as between type 3 deiodinase and type 1 11β-hydroxysteroid dehydrogenase, were observed. Taken together, the results indicate that responses of the rat pituitary-adrenal axis to calorie deficit are age-dependent. Moreover, the observed correlations suggest a mechanism linking an increase in glucocorticoid receptors with a reduction in peripheral thyroid hormone action resulting from a rise in the level of type 3 deiodinase.