Glucocorticoid receptors in patients with congenital adrenal hyperplasia

To determine the glucocorticoid receptor (GC-R) status in congenital adrena l hyperplasia (CAH) we examined 11 patients (5 female, 6 male) with 21-hydr oxylase deficiency and 3 patients (2 female, 1 male) with 11 beta -hydroxyl ase deficiency, The mean age at investigation was 8.9+/-3.5 yr, Age of diag nosis was 4.4+/-3.2 yr and all patients were being treated with hydrocortis one, The control group included 10 (5 female, 5 male) age-matched healthy c hildren. Blood samples were drawn at 0800 a.m. after an overnight fast in a ll subjects and after 5 days off treatment in patients with CAH. Serum cort isol tin all children), and serum 17-hydroxyprogesterone and androstenedion e tin the patient group) were measured by radioimmunoassay, Mononuclear leu kocytes were isolated from peripheral blood and the binding of [H-3]dexamet hasone to GC-R was examined. GC-R number and the dissociation constant (Kd) , which is inversely proportional to its binding affinity, were determined, Mean GC-R numbers were 5814+/-1574 and 6816+/-1647; mean Kd values were 3. 6+/-1.5 nM and 4.2+/-0.7 nM in patient and control groups, respectively, Th ere were no significant differences in these parameters between the two gro ups. Neither receptor number nor binding affinity correlated with basal ser um cortisol levels in either group. In the patient group, no correlation wa s observed between replacement hydrocortisone doses and either morning seru m cortisol levels or GC-R number, The higher binding affinity and requireme nt of higher hydrocortisone dose might have been due to a compensatory resp onse to increased clearance of glucocorticoids, In conclusion, GC-R paramet ers are not changed in patients with CAH and the variability of glucocortic oid replacement doses may be related to other functional defects of GC-R an d glucocorticoid pharmacokinetics.