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The role of pregnenolone sulphate in adrenal steroid biosynthesis and the ability of the human adrenal gland to synthesize and secrete dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulphate (DHA sulphate) was investigated. The presence of pregnenolone sulphate and DHA sulphate was demonstrated by measuring their concentrations in human adrenal tissue. Pregnenolone sulphate was metabolized in vitro mainly to free steroids, including DHA and cortisol, as well as directly to DHA sulphate in some cases. Similar results were obtained upon perfusion of the adrenal gland in situ with [¹⁴C]pregnenolone and [³H]pregnenolone sulphate as the substrates and isolating the metabolites from the adrenal venous blood. Dehydroepiandrosterone sulphate was derived mainly from the sulphation of free DHA. The hydrolysis of DHA sulphate did not appear to make a significant contribution to the amounts of DHA synthesized under these conditions.

The adrenal secretion of DHA and DHA sulphate by eight patients undergoing adrenalectomy was determined by measuring the concentrations of these compounds in samples of adrenal and peripheral venous blood taken simultaneously. In one patient secretion of DHA and DHA sulphate was equivalent whilst in the remainder there was much greater secretion of DHA.

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