Abstract
Plasma levels of corticosrerone measured at various times after the i.v. injection of various doses of corticosterone suggest that some of the steroid is relatively protected from metabolism (bound) and some is metabolized more rapidly (free or loosely bound). Moreover, the endogenous steady-state is disturbed by the injection, and tracer corticosterone probably does not reach equilibrium with the total body pool. The steady-state is nonexistent after rapid i.v. injection. Hence estimates of the half-life of plasma corticosterone are too low, and calculations of rate of synthesis are too high. Intravenous infusion of tracer quantities of corticosterone to the steady state is a more accurate method for estimating half-life and, also, the rate of synthesis of corticosterone. Metyrapone, an inhibitor of steroid synthesis, produced a biphasic disappearance curve of endogenous plasma corticosterone, indicating at least two pool distribution. The half-life of the second exponential phase is similar to that obtained by the infusion of labeled steroid. Phenobarbital, an inducer of liver microsomal reduced nicotinamide adenine dinucleotide phosphate enzymes, one or more of which metabolize adrenal steroids, increases the rate of metabolism of corticosterone (decreased steady-state level and decreased half-life of tracer) but plasma levels of endogenous steroid are maintained at control levels or higher by a compensatory increase in the calculated rate of synthesis.
Footnotes
- Received April 8, 1971.
- Accepted June 22, 1971.
- © 1971 by The Williams & Wilkins Co.
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