Thomas Strasser

Mineralocorticoid and Glucocorticoid Receptors in Circulating Mononuclear Leukocytes of Patients with Primary Hyperaldosteronism

Mineralocorticoid and glucocorticoid receptors were measured in circulating mononuclear leukocytes in 5 patients affected by Conns syndrome (3 cases of bilateral adrenal hyperplasia and 2 cases of adenoma plus unilateral hyperplasia). The number of the binding sites per cell resulted significantly lower (189 +/- 114, mean +/- SD), as compared with the normal controls (298 +/- 105). The affinity of aldosterone for the receptor was found to be not different than that of healthy control subjects. The capacity and the affinity of dexamethasone for glucocorticoid receptors ranged in the normal values. These data suggest a possible down-regulation of mineralocorticoid receptors in humans.

Parallel determination of glucocorticoid receptors in human mononuclear and polymorphonuclear leukocytes after Percoll separation

Circulating human leukocytes are known to possess glucocorticoid receptors, but the data in the literature on the affinity and capacity widely range. We here report our results on the determination of affinity and capacity of glucocorticoid receptors in both mononuclear and polymorphonuclear leukocytes using a Percoll gradient for separating cells. The mean affinity of mononuclear and polymorphonuclear cells was respectively 4.3 ± 0.7 and 4.3 ± 1.5 nM (mean ±S.D., n = 6), and the capacity 4135 ± 1950 and 1810 ± 832 sites per cell. Previous reports using a Ficoll separation showed a lower affinity under the same conditions of incubation. From these findings we suggest that the separation with Percoll may give values closer to physiological than other separation techniques.

Polymorphonuclear leukocyte 5-lipoxygenase activity in psoriasis

5-lipoxygenase-derived products of arachidonic acid are implicated in the pathophysiology of psoriasis, a common hyperproliferative and inflammatory skin disease. We therefore examined whether there is an activation of this enzymatic pathway in extracutaneous tissues. For this purpose, we measured the conversion of 14C-arachidonic acid by polymorphonuclear leukocytes from psoriatic patients and controls. No significant difference in the generation of leukotriene B4 and 5-hydroxyeicosatetraenoic acid by polymorphonuclear leukocytes was noted between the two groups. We conclude that in psoriasis there is no enhanced activity of the 5-lipoxygenase pathway in circulating polymorphonuclear leukocytes.

THE DETERMINATION OF MINERALOCORTICOID RECEPTORS IN HUMAN MONONUCLEAR LEUKOCYTES FROM PATIENTS WITH MINERALOCORTICOID EXCESS: PHYSIOLOGICAL AND PATHOLOGICAL IMPLICATIONS

The affinity and the capacity of mineralocorticoid receptors (MR) in human mononuclear leukocytes (HML) were determined in 9 patients with Conns syndrome (PA) and in 3 patients with pseudohypoaldosteronism (PHA). The number of binding sites per cell was 136 +/- 39 (mean +/- SD) in PA. One case with PHA had no MR, and of the other 2 patients, one had 50 and the other 55 receptors per cell. The capacity of normal controls ranged from 200 to 400 receptors per cell (n = 20). We conclude that the etiology of PHA is due to a lack of MR in the target tissues and that a down regulation of MR may exist in PA.

81 DEMONSTRATION OF MINERALOCORTICOID RECEPTOR DEEICIENCY IN TWO SIBLINGS WITH PSEUDOHYPOALDOSTERONISM(PH)

Aldosterone(A) binding sites have been demonstrated in human mononuclear leucocytes(HML).The measurement of the mineralocorticoid binding capacity of these receptors could be a valuable tool to assess states of mineralocorticoid insensitivity in humans.We here present data obtained in 2 sibs with PH and their parents. The 8 y old girl was diagnosed in infancy after a severe salt-losing crisis. Plsma renin activity(PRA) and A were elevated. In the 2 y old brother the diagnosis was suspected when hyponatraemia and hyperkalaemia occured in the first week of life. At this time PRA and A were normal but became elevated at 3months of age. Both children receive oral sodium supplementation, the dosage needed to normalize the sodium balance in the girl is considerably higher than in the younger brother. The parents show no signs of sodium imbalance.When measuring the A binding in HML we found no binding sites in the girl. In the boy, there were 62 receptors/cell (r/c) as compared to 170±29 r/c in normal children. The binding sites in the parents were within the normal adult range. These results are strong evidence that the A insensivity in PH is due to a deficiency of mineralocorticoid receptors. It may be speculated that this deficiency is also present in other mineralocorticoid target organs in particular in the kidney. The existence of a small amount of receptor in the boy may explain the more favorable course in this child.