ABSTRACT
Corticotropin-releasing hormone (CRH) levels in the human plasma and cerebrospinal fluid (CSF), and those in the rat hypothalamus, peripheral and hypophyseal portal plasma were studied by a specific h/r CRH RIA and an immunoaffinity procedure. CRH levels in the plasma and CSF were low in patients with hypercortisolemia and those with hypothalamic hypopituitarism, but high in patients with hypocortisolemia except for patients with hypothalamic hypopituitarism. Plasma CRH responded to insulin-induced hypoglycemia (ITT) those with Addison's disease and those with primary hypopituitarism, but not in patients with Cushing's syndrome or in patients with hypothalamic hypopituitarism. The results suggest that the major component of plasma CRH may be of hypothalamic origin, but other extrahypothalamic tissues cannot be ruled out as minor sources of plasma CRH. In addition, the measurement of CRH levels in the plasma and CSF seems to be of value in evaluating the hypothalamic function. The short negative feedback mechanism regulating CRH release was demonstrated in humans and rats. In the absence of the long negative feedback control of ACTH secretion by glucocorticoids, ACTH originating from the pituitary may regulate ACTH secretion form the pituitary through inhibition of CRH release.
Subject(s)
Corticotropin-Releasing Hormone/analysis , Addison Disease/blood , Addison Disease/cerebrospinal fluid , Addison Disease/metabolism , Animals , Corticotropin-Releasing Hormone/blood , Corticotropin-Releasing Hormone/cerebrospinal fluid , Cushing Syndrome/blood , Cushing Syndrome/cerebrospinal fluid , Cushing Syndrome/metabolism , Humans , Hypopituitarism/blood , Hypopituitarism/cerebrospinal fluid , Hypopituitarism/metabolism , Hypothalamus/analysis , Hypothalamus/metabolism , Immunoassay , Nelson Syndrome/blood , Nelson Syndrome/cerebrospinal fluid , Nelson Syndrome/metabolism , Pituitary Gland/analysis , Pituitary Gland/metabolism , Radioimmunoassay , Rats , Reference Values , Tissue DistributionABSTRACT
The concentrations of immunoreactive corticotropin-releasing factor (I-CRF) in human cerebrospinal fluid (CSF) were measured utilizing immunoaffinity chromatography and RIA in patients with no endocrine disease, patients with Cushing's disease, Nelson's syndrome, Sheehan's syndrome, Addison's disease and steroid treated patients. On high performance liquid chromatography, the elution profile and retention time of I-CRF in CSF were not identical with ovine CRF. I-CRF concentrations in CSF from patients with Cushing's disease and Sheehan's syndrome were lower than those from normal subjects, however those from patients with Nelson's syndrome and Addison's disease were within the normal range. I-CRF concentrations in CSF from patients with Cushing's disease returned to normal levels 2-9 months after pituitary adenomectomy. These results suggest that CSF I-CRF concentrations are reduced by increased plasma corticosteroid levels.
