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 C ' F 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<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. Therefore, our results suggest that hypothalamic CRF metabolism in Cushing's disease is suppressed with the elimination of its diurnal activity by secondary hypercortisolism due to autonomic ACTH-hypersecretion from pituitary adenoma.