Corticotropin-releasing factor concentrations in cerebrospinal fluid and its diurnal rhythm in patients with Cushing's disease

Abstract

Since Vale et al isolated and sequenced a 41 amino acid peptide with corticotropin-releasing factor (CRF) activity from ovine hypothalami, intensive works have been done about its physiological activity and intracerebral distribution. However, little has been done yet about CRF metabolism in human cerebrospinal fluid (CSF). Using a specific ovine CRF radioimmunoassay (RIA), we measured the levels of CRF in CSF from 16 patients with Cushing's disease (group I), 8 patients with Acromegaly (group II), 5 patients with Prolactinoma (group III) and 10 patients without endocrine abnormalities (group IV). Moreover diurnal changes of CRF in CSF from 2 patients with Acromegaly and 2 patients with Cushing's disease were examined. Dilution curves of CRF in CSF were parallel to that of synthetic ovine CRF standard. The intraassay coefficient of variation was 9.2% and the interassay coefficient of variation 12.6%. The concentrations of CRF in CSF of groups I, II, III and IV were 38.83 +/- 9.02 pg/ml (mean +/- SD), 44.24 +/- 4.71, 47.62 +/- 8.05 and 49.45 +/- 12.86, respectively. Group I was significantly lower than group IV (p less than 0.05). On the other hand, group II or III was not significantly different from group IV. A diurnal rhythm of CRF in CSF was observed in 2 patients with Acromegaly. However, there was almost no change in the 2 patients with Cushing's disease. In considering rich amount of CRF in hypothalamus and CRF-positive fibers surrounding the third ventricle, CRF content in CSF seems to reflect mainly its metabolic activity in hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)