THE EFFECT OF ESTROGEN ADMINISTRATION ON THE METABOLISM AND PROTEIN BINDING OF HYDROCORTISONE

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Abstract
A study has been made of the effect of estrogen administration on the plasma hydrocortisone level in normal subjects, with and without concomitant cortisone therapy. Plasma hydrocortisone levels in some instances fall progressively during the control period with cortisone alone. This is reversed by administration of estrogen. By use of ultrafiltration at 37[degree] C. and double isotope tracer techniques the protein-bound and nonprotein-bound fractions of plasma hydrocortisone were studied. Approximately 5-10 per cent was not protein bound. This percentage was reduced, but absolute values remained the same, when estrogen was given. The rise in the plasma level of hydrocortisone represented an increase in the protein-bound fraction, and in vitro techniques revealed an increase in the binding protein, or in the number of sites. The increased plasma levels due to estrogen therapy were not associated with depression of eosinophils, which suggests that only the nonprotein-bound fraction is biologically active. The half-time for disappearance of plasma hydrocortisone is considerably prolonged by administration of estrogen; this probably represents protection from destruction by the liver by means of greater protein binding. The effects of estrogen in altering hydrocortisone metabolism are comparable to those produced by pregnancy.