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Glucocorticoids decrease a binding of corticotropin-releasing hormone-binding protein in human plasma
1Department of Medicine, Tokyo Women's Medical College, Japan.
Insights
Glucocorticoids reduce corticotropin-releasing hormone-binding protein (CRH-BP) levels in plasma. This study investigated CRH-BP binding in patients with adrenal disorders, finding altered levels linked to cortisol concentrations.
Area of Science:
- Endocrinology
- Hormone Research
- Clinical Diagnostics
Background:
- Corticotropin-releasing hormone-binding protein (CRH-BP) plays a role in regulating the hypothalamic-pituitary-adrenal (HPA) axis.
- Plasma CRH-BP levels and binding are altered in various HPA disorders.
Purpose of the Study:
- To investigate the binding of CRH-BP to human CRH in patients with HPA axis disorders.
- To explore the relationship between CRH-BP binding, cortisol levels, and glucocorticoid treatment.
Main Methods:
- Examined CRH-BP binding in plasma of patients with Cushing's syndrome, Addison's disease, and hypopituitarism.
- Utilized labeled human CRH for binding assays.
- Performed Scatchard analysis to assess binding affinity and site number.
Main Results:
- CRH-BP binding was decreased in Cushing's syndrome and with long-term high-dose glucocorticoid treatment.
- CRH-BP binding was increased in Addison's disease and hypopituitarism.
- Glucocorticoid replacement normalized increased CRH-BP binding in Addison's disease.
- A negative correlation was observed between plasma cortisol and CRH-BP binding in Cushing's syndrome.
- Scatchard analysis indicated reduced CRH-BP binding sites in Cushing's syndrome patients.
Conclusions:
- Glucocorticoids appear to decrease CRH-BP binding in human plasma, likely by reducing CRH-BP concentration.
- Altered CRH-BP binding is a characteristic of hypercortisolemia and other HPA axis dysregulations.
Abstract:
The binding of CRH-binding protein (CRH-BP) in plasma to labeled human CRH has been examined in patients with hypothalamic-pituitary-adrenal disorders. Compared with that in normal subjects, CRH-BP binding decreased in patients with Cushing's syndrome of pituitary or adrenal origin and in patients who were treated with a high dose of glucocorticoids over a long period of time. On the other hand, CRH-BP binding increased in patients with Addison's disease or hypopituitarism. In patients with Addison's disease, the high level of CRH-BP binding fell to the control level after glucocorticoid replacement. In patients with Cushing's syndrome, CRH-BP binding gradually increased and reached the higher level about 1 yr after surgery. Thereafter, it returned to the control level. There was a good negative correlation between the levels of plasma cortisol and CRH-BP binding in patients with Cushing's syndrome before and after surgery. A Scatchard analysis of CRH-BP binding in patients with Cushing's syndrome and in normal subjects showed that the binding affinity was similar in both groups, but that the number of binding sites was low in patients with Cushing's syndrome. These results suggest that in human plasma, glucocorticoids decrease CRH-BP binding. This seems to be caused by a decrease in the concentration of CRH-BP in the plasma of patients with hypercortisolemia.