Studies on the Metabolism of Blood-Borne Cholesterol Sulfate^*

Abstract

Using isotopic dilution techniques, certain metabolic properties of cholesteryl 3/3-sulfate [cholesterol sulfate (CS)], a substance that has recently been isolated from human blood and adrenal tissue, were studied in two normal human subjects. Thus, the concentration (c) of circulating CS" in the plasma was found to be 328 and 924 jug/100 ml. Following the injection of [14C]CS, the metabolic clearance rate (MCR) of this compound was determined from the disappearance curve of the tracer from plasma. From these data, the half-life was calculated to be 14-15 hr in these subjects. The production rate of cholesterol c X^>holesterol sulfate (CS)* 1 *has recently been shown by Drayer et al. (1964) to be a naturally occurring entity. This conjugate has been found in bovine adrenal tissue, human blood (Drayer et al., 1964), and adrenal tumor tissue (N. M. Drayer, unpublished data). Recently, Moser et al. (1966) also isolated this sulfate from natural sources. That CS may serve, too, as a substrate for the mitochondrial side-chain cleaving enzyme of bovine adrenal tissue has been described by Raggatt et al. (1965). Moreover, Roberts et al. (1964) perfused CS through a human adrenal adenoma, in situ, and the results suggest that CS was converted to a variety of A5-3/3-sulfated steroids via intermediates which retain the sulfate grouping. The purpose of the present study was to determine the plasma concentration of CS, the rate at which blood-borne CS is produced (PRcs), and the quantitative importance of circulating CS as a precursor of steroids. Values for the metabolic clearance rate, MCR, were obtained by injecting 14C-labeled CS intravenously and measuring the concentration of radioactivity present as CS in plasma samples withdrawn at various intervals fol-

Cholesterol sulfate in human physiology: what's it all about?

“…The apparent validity of this initial value was soon confirmed by reports of plasma cholesterol sulfate levels involving a limited number of subjects that ranged from 174 to 328 g/100 ml (31)(32)(33). Studies involving larger groups of subjects but utilizing different methodologies revealed plasma cholesterol sulfate levels in normal subjects of 150-250 g/ml (34,35), 178 Ϯ 31 g/100 ml (men and women) (36), 134-322 g/ml (men) and 117-214 g/ ml (women) (37), 118-138 g/ml (men) (38), 272 Ϯ 64 g/ml (men) and 175 Ϯ 70 g/ml (women) (39), 134 Ϯ 29 g/ml (men) (40), and 253 Ϯ 25 g/ml (women) (41).…”

“…Production rates (PRs) of cholesterol sulfate have not been evaluated extensively, but, based on estimated metabolic clearance rates (MCRs) and plasma steroid/sterol concentrations ([S]), PRs (PR ϭ MCR ϫ [S]) of 35 mg/ day and 163 mg/day were determined for two normal subjects (31). Interestingly, the PR for cholesterol sulfate appears to be comparable to the PR of ‫ف‬ 45 mg/day determined for the other prominent circulating steroid sulfate, i.e., DHEA sulfate.…”

“…The latter PR was calculated for young men from reported DHEA [S] and MCR values (47,63). It should be noted that, in contrast to their unconjugated counterparts, cholesterol sulfate and DHEA sulfate are cleared slowly from the circulation with MCRs, respectively, of 10-17 l/day and 15-30 l/day (31,64). The slow clearance of these steroid sulfoconjugates from the circulation reflects their tight binding to plasma proteins, especially albumin (65).…”

Identification of a novel sulfonated oxysterol, 5-cholesten-3β,25-diol 3-sulfonate, in hepatocyte nuclei and mitochondria

“…Several sulfonated sterols have been reported to be widely distributed in steroidogenic tissues (26) and to circulate in plasma at concentrations ranging from 328 to 924 mg/100 ml, with a blood production rate of 35-163 mg/day (27). A similar sulfonated oxysterol derivative, 24-hydroxycholeterol 3-sulfonate 24-glucuronide (based on MS/MS analysis), was reported in the serum and urine of children with severe cholestatic liver diseases (26).…”

Metabolism of deoxycorticosterone and deoxycorticosterone sulfate in men and women.

“…The C-21-sulfate bears some analogy to the sulfurylated side chain of the bile acids. Recently, we have found (unpublished observations) that the metabolic clearance rate of plasma DOC-SO4 is quite high (650-1,000 liters/24 h) compared with that of other steroid sulfates; e.g., the metabolic clearance rate of plasma dehydroisoandrosterone sulfate (26) and cholesteryl sulfate (27) in men and nonpregnant women is only 10 liters/24 h and those of estrone sulfate (28,29), pregnenolone sulfate (30), and testosterone sulfate (31) are of the order of 150 liters/24 h. This may be due to preferential entry into bile of steroid-21-sulfates compared to steroid-3d-sulfates or steroid-17f3-sulfates or else due to bacterial metabolism of DOC-SO4 in a manner that precludes reabsorption of DOC-SO4 and thus constitutes irreversible metabolism (i.e., conversion to progesterone and metabolites thereof). It has been shown that the rate of entry of dehydroisoandrosterone sulfate into bile is slow (32).…”