Ovine (o) and human (h) corticotrophin releasing factor (CRF) in man: CRF-stimulation and CRF-immunoreactivity

The biological activity of ovine (o) and human (h) corticotrophin releasing factor (CRF) in normal volunteers was investigated. Nine subjects received an iv bolus injection of 50, 100 and 200 micrograms oCRF. There was no dose-response relationship between the injected oCRF dosage and stimulated ACTH, beta-endorphin, and cortisol secretion. The addition of glycine as a stabilizer to 50 and 100 micrograms oCRF had no effect on stimulated ACTH and cortisol secretion. When 50 and 100 micrograms hCRF were injected into the same subjects no significant difference compared to the oCRF induced ACTH-response was observed. In contrast to the lacking relationship between the CRF dosage and the biological response there was a clearcut dose-response relationship between the amount of oCRF injected and CRF-immunoreactivity 15 min after injection measured with a specific oCRF radioimmunoassay. Though there was only 10% cross-reactivity with synthetic hCRF, endogenous CRF-immunoreactivity could be detected in 53 of 55 pregnant females and in placental extracts. The fact that endogenous CRF immunoreactivity in humans measured by the oCRF-system may be due to the CRF molecule could be supported by identical elution profiles of synthetic and endogenous hCRF which eluted less retarded than oCRF from the Sephadex column. Our data suggest that the already established stimulation-test with oCRF can be replaced in the future by a test using human material in an identical dosage. In addition determination of endogenous CRF seems to be feasible, particularly with the homologous human system and may be of use in evaluation of patients with pituitary adrenal diseases.