Rapid and opposite effects of cortisol and estradiol on human erythrocyte Na+,K+-ATPase activity: Relationship to steroid intercalation into the cellmembrane

We determined whether two naturally occurring steroids, cortisol and 17 bet a-estradiol (E-2), can rapidly modulate the activity of an important membra ne protein, human erythrocyte (RBC) Na+,K+-ATPase, an enzyme that does not bind either hormone directly. We also determined the membrane binding locat ions for cortisol and E-2 and their effects on membrane molecular structure and fluidity. Direct application of both steroids to intact human RBC sign ificantly altered maximum ouabain-sensitive Rb-86 uptake within 5 min: Cort isol decreased it by 24% whereas E-2 increased it by 18%. As determined by small angle x-ray diffraction, these steroids occupied distinct time-averag ed binding locations in the RBC membrane, cortisol localizing near the bila yer surface, 14-29 Angstrom from the bilayer center, and E-2 localizing dee p within the hydrocarbon core, 0-7 Angstrom from the bilayer center. Neithe r steroid significantly changed overall bilayer width or membrane fluidity. These data suggest that cell membrane protein function can be altered rapi dly and differentially by naturally occurring steroids. This effect did not appear to be related to the different binding locations of the steroids in the membrane or to their influence on membrane fluidity.