Synthesis of Dehydroepiandrosterone and Dehydroepiandrosterone Sulphate by the Human Adrenal

Abstract

The role of pregnenolone sulphate in adrenal steroid biosynthesis and the ability of the human adrenal gland to synthesize and secrete dehydroepiandrosterone (DNA) 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 [13H]prenenolone 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 adrenal-ectomy 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.

Dehydroepiandrosterone Sulfate Decreases the Interleukin-2-Mediated Overactivity of the Natural Killer Cell Compartment in Senile Dementia of the Alzheimer Type

“…The adrenal gland is the major source of the circulating steroidal product dehydroepiandrosterone and its conjugate ester dehydroepiandrosterone sulfate (DHEAS) [1][2][3]. Although DHEAS represents the most abundant steroid in blood, its physiological activity is still unknown.…”

Dehydroepiandrosterone Sulfate Enhances Natural Killer Cell Cytotoxicity in Humans Via Locally Generated Immunoreactive Insulin-Like Growth Factor I1

“…D EHYDROEPIANDROSTERONE (DHEA) and its conjugate ester dehydroepiandrosterone sulfate (DHEAS) are synthesized and released from the adrenal gland and are associated with multiple functional changes in humans (1)(2)(3)(4)(5)(6)(7)(8). Concerning the effects on immune regulation, DHEA and DHEAS appear to have some beneficial influences on immunity, by increasing cell proliferation and the production of cytokines from immune cells and by decreasing the immunosuppressive action of glucocorticoids (8 -16).…”

Unique plasma metabolomic signature of osteonecrosis of the femoral head

“…In our study, abnormalities of the corticosteroid‐related pathway were detected in ONFH samples compared with control groups, with compounds such as pregnenolone, 21‐hydroxypregnenolone disulfate, DHEA‐S, epiandrosterone sulfate, and androsterone sulfate affected, most of which were down‐regulated in ONFH samples. These are all essential intermediates for corticosteroid synthesis . Serum DHEA‐S is regarded as a classic marker of the individual hormonal milieu .…”

“…These are all essential intermediates for corticosteroid synthesis. [33][34][35] Serum DHEA-S is regarded as a classic marker of the individual hormonal milieu. 36 Abnormal expression of DHEA-S has been detected in several pathological conditions, including decreased bone density, increased cardiovascular disease, and elevated fat-to-muscle ratio.…”