ENDOGENOUS OUABAIN SECRETION IN MAN IS NOT REGULATED BY ACTH

It has been suggested that endogenous ouabain-like substance (OLS) is of adrenal origin and the secretion of OLS may be ACTH dependent. To d etermine if OLS is influenced by the pituitary-adrenal axis, we studie d the effect of adrenal stimulation (0.25 mg Synacthen) and suppressio n (1 mg Dexamethasone) on two separate groups of nine subjects. Serum OLS was measured by a radioimmunoassay (RIA) developed in our lab, and cortisol and ACTH were measured by commercial assay kits. Dexamethaso ne significantly (P < 0.001) suppressed serum cortisol and ACTH concen trations, without effecting endogenous OLS concentration (0.64+/-0.17 vs 0.85+/-0.18nmol/l). Synacthen increased the concentration of cortis ol in serum (p < 0.001) over the test period; OLS concentration, again , remained unchanged (0.45 +/- 0.04 vs 0.43 +/- 0.05 nmol/l). In furth er studies, serum concentrations of cortisol and OLS were compared bet ween left (LAV) and right (RAV) adrenal veins with that from the infer ior vena cava (IVC). Concentration of cortisol in the LAV and RAV was five-fold greater than that in IVC. However, there was no difference i n OLS concentration at the corresponding sites. In addition, serum OLS concentrations in patients having undergone bilateral adrenalectomy o r diagnosed with Addison's disease (0.62 +/- 0.19 nmol/l) were similar to concentrations in healthy subjects (0.67 +/- 0.21 nmol/l). Examina tion of bovine adrenal, liver, kidney, heart and human placenta demons trated that OLS content of bovine adrenal was comparable with other ti ssues analysed. HPLC studies of human serum and bovine adrenal gland p roduced identical elution profiles, resolving a single peak which coin cided with the retention time observed for standard ouabain. We conclu de that the adrenal is unlikely to be the source of endogenous OLS, th e secretion of which appears to be independent of ACTH. (C) 1998 Elsev ier Science Ltd. All rights reserved.