Effect of intravenous infusions of corticosterone and 11-deoxycortisol on the plasma glucocorticoid profile in normal adult subjects

Abstract

Simultaneous comparison of plasma levels of Cortisol, cortisone, corticosterone, and 11-deoxycortisol was performed in healthy adult volunteers of both sexes before, during and after intravenous infusion of corticosterone and 11-deoxycortisol, respectively. Chromatographic separation on Sephadex LH-20 columns was used prior to steroid quantification by specific protein binding assays. Steroids were infused at the dose of 10 mg/h/60 ml saline; 6 subjects underwent corticosterone infusion from 22:00 to 04:00; 4 subjects underwent 11-deoxycortisol infusion from 22:00 to 04:00; 4 subjects underwent 11-deoxycortisol infusion from 24:00 to 08:00. To obtain control data, saline alone was always infused under the same conditions on the preceding day. Blood samples were drawn at different intervals; in each subject, attention was given to obtain samples at the following hours: 04:00, 08:00, 12:00, 16:00, 20:00, and 24:00. Under control conditions, clear circadian fluctuations were observed for Cortisol, cortisone, and corticosterone; levels of 11-deoxycortisol did not show significant changes along the 24-h day. Corticosterone infusion did consistently interfere with the morning rise of plasma Cortisol and cortisone; levels of Cortisol were significantly reduced in comparison to control values at 04:00, 08:00, and 12:00 (p<0.01). The circadian rhythm of the circulating Cortisol was not abolished, but its amplitude was diminished to about 60% of the control values. On the contrary, exogenously administered 11-deoxycortisol did not affect plasma concentrations of other examined steroids in both experimental infusions. It is suggested that corticosterone when intravenously infused at pharmacological doses during the nocturnal hours has a limited ACTH-suppressing potency whereas 11-deoxycortisol under the same conditions has no effect. Displacement of Cortisol molecules from the transcortin binding sites may be a complementary factor in accounting for the effect of corticosterone on the plasma glucocorticoid profile.