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Estrone sulfate, quantitatively the most important estrogen in plasma, has previously been determined only after hydrolysis and chromatography. An antiserum raised against estrone glucosiduronate-bovine thyroglobulin was found to be suitable for the specific RIA of estrone sulfate both in plasma and urine. Plasma levels were measured after solvent extraction without hydrolysis or chromatography. The mean (+/-SE) was 972 +/- 79 pg/ml (range, 537-1581) in 15 women in the follicular phase, 1806 +/- 160 pg/ml (range, 814-3358) in 15 women in the luteal phase, and 922 +/- 62 pg/ml (range, 461-1238) in 13 men. The urinary excretion of estrone sulfate, measured after simple chromatographic separation, ranged from 0.8-7.9 micrograms/24 h in men and 5.1-18.7 micrograms/24h in nonpregnant women. This was generally one-seventh to one-half the simultaneous estrone glucosiduronate excretion rate. An approximate mean renal clearance of estrone sulfate calculated from the above values was 2.7 ml/min. The low clearance rate is taken to reflect extensive binding of estrone sulfate by plasma proteins. The splanchnic extraction of estrone sulfate measured in 6 patients undergoing hepatic vein catheterization for diagnostic purposes was 29.8 +/- 11.1%, indicating net uptake of this compound by the splanchnic area.

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Specific RIAs requiring ether extraction only were established for estrone and 17 beta-estradiol both in plasma and in urine from the nonpregnant female. These assays were used to measure the renal clearance rates of estrone and of 17 beta-estradiol in eight ambulatory women in the follicular and in the luteal phases of the menstrual cycle. The mean (+/-SE) for the renal clearance rate of estrone was 0.71 +/- 0.058 ml/min in the follicular phase and 1.26 +/- 0.35 ml/min in the luteal phase. The mean (+/-SE) renal clearance rate of 17 beta-estradiol was 0.44 +/- 0.055 ml/min in the follicular phase and 0.29 +/- 0.043 ml/min in the luteal phase. There was no significant difference in the renal clearance rates of either estrone or of 17 beta-estradiol between the follicular and luteal phases of the cycle. The renal clearances of estrone and 17 beta-estradiol were highly correlated (r = 0.84; P less than 0.01). The renal clearance rate of estrone was significantly greater than that of 17 beta-estradiol in both phases of the cycle (P less than 0.01).