Identification and characterization of a human corticosteroid binding globulin variant with a reduced affinity for cortisol.
A corticosteroid binding globulin variant (CBGv) has been identified in a serum sample taken from an apparently healthy woman during late pregnancy. Identification was based on the observation that it exhibited approximately half the cortisol binding capacity expected when compared to its concentration measured by radioimmunoassay (RIA). Affinity purification of CBGv excluded the possibility that this anomaly was caused by assay interference, and demonstrated that immunoreactive CBGv was capable of binding cortisol. The CBGv had a molecular weight (63 800) similar to normal CBG, and no evidence of molecular aggregation was found by gel filtration. Although the electrophoretic mobility, isoelectric profile and immunochemical identity of CBGv appeared to be similar to normal CBG, it focussed as two distinct bands (pI 5.48 and pI 5.53) after desialylation with neuraminidase, unlike normal CBG which focuses only at pI 5.48. Investigation of the steroid binding characteristics of CBGv revealed a reduced association-rate constant (Ka = 1.05 X 10(9) l/mol) and dissociation half-time (12.5 min) when compared with normal CBG (Ka = 1.39 X 10(9) l/mol and 25 min at 0 degree C) but an apparently normal steroid binding specificity. Although the physiological significance of this variant is not known, the cortisol concentration in the variant serum was within the normal range of women during late pregnancy. No other CBG variants were identified among other normal controls (n = 66) or nine patients with Cushing's syndrome. It is suggested that comparisons between cortisol binding capacity and RIA will reveal other variants of CBG, and lead to greater understanding of their physiological significance.
D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007525:Isoelectric Focusing; D011247:Pregnancy; D011863:Radioimmunoassay; D014156:Transcortin / Q000302:isolation & purification* / Q000378:metabolism
D014156:Transcortin; D006854:Hydrocortisone