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The early mineralocorticoid effector mechanism, the sodium—proton exchanger, is sensitized in lymphocytes from patients with Cushing's syndrome
Author(s) -
Wehling M.,
Käsmayr J.,
Christ M.,
Sippell W.,
Thelsen K.,
Müller O.A.
Publication year - 1992
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1992.tb02320.x
Subject(s) - endocrinology , aldosterone , medicine , mineralocorticoid , sodium , chemistry , stimulation , mineralocorticoid receptor , peripheral blood mononuclear cell , in vitro , biochemistry , organic chemistry
OBJECTIVE In‐vitro binding of aldosterone to mineralocorticoid receptors on human mononuclear leucocytes and its effects on the intracellular sodium and potassium concentrations, the sodium‐proton exchanger and cell volume of human mononuclear leucocytes have been described for normals. In the present paper this easily accessible human cell model was studied in Cushing's syndrome to detect abnormalities of the mineralocorticoid effector mechanism. DESIGN The rate of cell swelling in isotonic sodium propionate reflecting the activity of the sodium‐proton exchanger and the stimulatory activity of 1.4 nM aldosterone were determined in a Coulter Channelyzer. PATIENTS Nine female patients with pituitary‐dependent (7) and adrenal hypercortlsollsm (2) were included in the study. MEASUREMENTS Compared with controls from matched normals, the cell volume of human mononuclear leucocytes in a physiological buffer was significantly increased in the patients. The increment of cell size in isotonlc sodium propionate was elevated in the presence of 1.4 nM aldosterone only. RESULTS These findings are equivalent to an excess stimulation of the sodium‐proton exchanger by aldosterone in these patients. Plasma cortlsol was inversely correlated with the cell swelling In propionate. CONCLUSIONS These data indicate that the early mineralocorticoid effector mechanism in human mono‐nuclear leucocytes from patients with Cushing's syndrome has an increased sensitivity to aldosterone compared with that from normals. This could reflect an adaptation of the cellular electrolyte metabolism to the decreased mineralocorticoid activity balancing the increased glucocorticold activity. If representative of other cell systems, e. g. renal tubular cells, these findings would identify accompanying electrolyte disorders in these patients not as a side‐effect of glucocortlcolds, but as a result of an increased sensitivity to endogenous mlneralo‐corticolds.