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LUDWIG KORNEL, JAMES T. MOORE, INGE NOYES, Corticosteroids in Human Blood: IV. Distribution of Cortisol and Its Metabolites Between Plasma and Erythrocytes in Vivo, The Journal of Clinical Endocrinology & Metabolism, Volume 30, Issue 1, 1 January 1970, Pages 40–50, https://doi.org/10.1210/jcem-30-1-40
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Abstract
The role of erythrocytes in the metabolism of cortisol in vivo was investigated in 3 subjects who received iv injection of tracer cortisol-4-14C. Following administration of the tracer, blood was sampled at 15–30 min intervals for 2½ hr, and a large blood specimen was obtained at the end of this period. By means of a technique developed by us previously, the following steroid fractions were estimated in the separated and hemolyzed red cells, in a saline wash of red cells, carried out prior to their hemolysis, and in plasma: “free” steroids, “polar free” steroids, glucuronide conjugates, sulfate conjugates, and conjugates of a new type, distinctly different from the other 2. The results obtained revealed the following: 1) 14–20% of total blood radioactive steroids were “associated” with the red cells; 2) less than half of this amount was “loosely” bound to the cells, presumably adsorbed on the cells' surface, and easily removed from the cells by a brief saline wash; concentrations of various free and conjugated steroid fractions in this saline wash were similar to those in plasma; 3) more than half of the steroids “associated” with red cells were more firmly bound to the cells and were not removed from them by the saline wash (they were presumably either bound to the cell membrane or were in the cells); the concentrations of various free and conjugated fractions of these steroids were entirely different than those of plasma steroids: 75–85% of them were “free” (nonconjugated) compounds, more than ⅓ of them being more strongly bound to proteins than the ones in plasma; 15–25% were in a conjugated form; 4) of the conjugates, only 8–14% were glucuronides, whereas 20–26% were sulfates; the remaining 62–69% were of a new type, so far unidentified, possibly formed within the cells. Individual steroids present in each steroid fraction were identified in the large blood specimens drawn 2½ hr after the administration of the tracer. It is concluded that there is a differential uptake of various corticosteroid metabolites by red cells in vivo, this being either due to different permeability gradients of the cell membrane for various free and conjugated steroids, or due to different affinities of various steroid metabolites for binding by cell membrane or other cell components. This implies that erythrocytes constitute a separate metabolic compartment for cortisol, thus playing an important part in its metabolism.
