Glucocorticoid receptors in mononuclear blood cells and their correlation to endogenous and exogenous corticoids in healthy and asthmatic children.
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 degrees 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 corticoid-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Griese
M
M
Department of Paediatrics, University of Düsseldorf, Federal Republic of Germany.
Kusenbach
G
G
Lüsebring
K
K
Köster
W
W
Roth
B
B
Reinhardt
D
D
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism*; D001665:Binding Sites; D002648:Child; D002675:Child, Preschool; D003348:Cortisone / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D011239:Prednisolone / Q000627:therapeutic use; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
D000305:Adrenal Cortex Hormones; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D011239:Prednisolone; D003348:Cortisone; D006854:Hydrocortisone