Abstract
The number and affinity of glucocorticoid binding sites in peripheral mononuclear cells (MNC) of asthmatic and healthy children were determined by a whole cell (3H)dexamethasone binding assay at 37°C. Using HPLC determination, corresponding serum levels of non-protein-bound (free) cortisol, whole cortisol and cortisone as well as urine excretion of free cortisone and cortisol were assessed. The average number of binding sites (BS) per cell and the dissociation constant (KD) respectively, in atopic asthmatics (7768±666 BS/MNC resp. KD=17.2±2 nM) did not differ from the values measured in our control group (8333±691 BS/MNC resp. 25.4±4.8 nM). Within the age range 1 month-15.8 years neither age-dependent changes nor sex-related differences in the number of binding sites or the KD values could be detected. Active or currently inactive asthmatics, and patients under different antiasthmatic drug regimes, had similar binding sites on MNC. No differences in serum levels of cortisol, cortisone and free cortisol or in free cortisol and free cortisone of 24-h urine samples were found between healthy children and asthmatics. After a short course of prednisolone therapy for an acute severe asthmatic attack the number of glucocorticoid binding sites in peripheral MNC decreased to an average of 4632±421 BS/MNC, whereas the dissociation constant did not change significantly (14.5±3.6 nM). The corticod-hormone pattern in the serum, 24-h urine excretion, and the normal number and affinity of glucocorticoid receptors on peripheral MNC suggest that there is no primary, general impairment of glucocorticoid metabolism in asthmatic children. Short-term glucocorticoid administration resulted in suppression of endogenous corticoids to undetectable levels accompanied by down-regulation of glucocorticoid-receptor BS to about 55% of control levels.
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Abbreviations
- BS:
-
binding sites
- SEM:
-
standard error of the mean
- MNC:
-
mononuclear cell
- KD :
-
dissociation constant of (3H) dexamethasone
References
Ballard PL, Ballard RA (1974) Cytoplasmic receptor for glucocorticoids in lung of the human fetus and neonate. J Clin Invest 53:477–486
Böyum A (1968) A one-stage procedure for isolation of granulocytes and lymphocytes from human blood. Scand J Clin Lab Invest [Suppl] 97:51–89
Brodde OE, Beckenringh JJ, Michel MC (1987) Properties of beta-adrenoreceptors in circulating lymphocytes: comparison with beta-adrenoceptors in the human heart. Trends Pharmacol Scien 8:403–407
Fraser CM, Venter JC (1980) The synthesis of beta-adrenergic receptors in cultured human lung cells: induction by glucocorticoids. Biochem Biophys Res Commun 94:390–397
Hirata F, Schiffman E, Venkatasubramanian K, Salomon D, Axelrod J (1980) A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids. Proc Natl Acad Sci USA 77:2533–2536
Junker K (1983) Glucocorticoid receptors of human mononuclear leukocytes in vitro. J Clin Endocrinol Metab 57:506–512
Katz P, Zaytoun AM, Lee JH (1985) Characterization of corticosteroid receptors in natural killer cells: comparison with circulating lymphoid and myeoloid cells. Cell Immunol 94:347–352
Kerepesi T, Aranyi P (1985) Low levels of glucocorticoid binding sites in circulating lymphocytes of premature infants suffering from hyaline membrane disease. J Steroid Biochem 22:151–154
Körholz D, Seger K, Griese M, Wahn V, Reifenhäuser A, Reinhardt D (1988) Beta-adrenoceptor density and resolution of high and low affinity state on B- and T-cells in asthmatic and non-asthmatic children. Eur J Pediatr 147:116–120
Kontula K, Pelkonen R, Andersson L, Sivula A (1980) Glucocorticoid receptors in adrenocorticoid disorders. J Clin Endocrinol Metab 51:654–661
Lacroix A, Bonnard GD, Lippman ME (1984) Modulation of glucocorticoid receptors by mitogenic stimuli, glucocorticoids and retinoids in normal human cultured T cells. J Steroid Biochem 21:73–80
Lippman M, Barr R (1976) Glucocorticoid receptors in purified subpopulations of human peripheral blood lymphocytes. J Immunol 118:1977–1981
Morris HG (1985) Mechanisms of action and therapeutic role of corticosteroids in asthma. J Allergy Clin Immunol 75:1–14
Nakazawa T, Umegae Y, Matsui S, Yoshie Y, Fueki R, Robayashi S (1986) Serial changes of plasma cortisol levels during various types of asthmatic responses due to allergen inhalation. Ann Allergy 56:67–71
Peterson AP, Altmann LC, Hill JS, Gosney K, Kadin M (1981) Glucocorticoid receptors in normal human eosinophils: comparison with neutrophils. J Allergy Clin Immunol 68:212–217
Piper P (1984) Formation and actions of leukotrienes. Physiol Rev 64:744–761
Rajpert E, Kalacinsiki W (1984) Glucocorticoid receptors in peripheral blood lymphocytes in asthmatic children during treatment. Pediatr Pol 59:95–100
Reinhardt D, Becker B, Nagel-Hiemke M, Schiffer R, Zehmisch T (1983) Influence of beta-receptor-agonists and glucocorticoids on alpha- and beta-adrenoceptors of isolated blood cells from asthmatic children. Pediatr Pharmacol 3:293–302
Reinhardt D, Zehmisch T, Becker B, Nagel-Hiemke M (1984) Age-dependency of alpha- and beta-adrenoceptors on thrombocytes and lymphocytes of asthmatic and nonasthmatic children. Eur J Pediatr 142:111–116
Rousseau GG, Baxter JD, Tomkins GM (1972) Glucocorticoid receptors: relation between steroid binding and biological effects. J Mol Biol 67:99–115
Sachs L (1984) Angewandte Statistik, 6th edn. Springer, Berlin Heidelberg New York Tokyo
Scatchard G (1949) The attractions of proteins for small molecules and ions. Ann NY Acad Sci 51:660–672
Schlechte JA, Ginsberg BH, Sherman BM (1982) Regulation of the glucocorticoid receptor in human lymphocytes. J Steroid Biochem 16:69–74
Slade JD, Hepburn B (1982) Prednisone-induced alterations of human lymphocyte subsets. J Lab Clin Med 101:479–487
Svec F (1985) Glucocorticoid receptor regulation. Life Sci 36:2359–2366
Szentivanyi A (1968) The beta-adrenergic theory of the atopic abnormality in bronchial asthma. J Allergy 42:203–232
Tsai BS, Watt G, Koesnadi K, Townley G (1984) Lymphocyte glucocorticoid receptors in asthmatic and control subjects. Clin Allergy 14:363–371
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M. Griese is a fellow of the Braun foundation, Melsungen, FRG
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Griese, M., Kusenbach, G., Lüsebring, K. et al. Glucocorticoid receptors in mononuclear blood cells and their correlation to endogenous and exogenous corticoids in healthy and asthmatic children. Eur J Pediatr 147, 490–495 (1988). https://doi.org/10.1007/BF00441973
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DOI: https://doi.org/10.1007/BF00441973