Corticotropin releasing factor: Basic studies and clinical applications

George P. Chrousos, Joseph R. Calabrese, Peter Avgerinos, Mitchel A. Kling, David Rubinow, Edward H. Oldfield, Thomas Schuermeyer, Charles H. Kellner, Gordon B. Cutler, Donald (Lynn) Loriaux, Philip W. Gold

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

1. 1. Corticotropin releasing factor (CRF) is a newly sequenced peptide first isolated from sheep hypothalami and thought to be an important modulator of both the pituitaryadrenal axis and the sympathetic nervous system. 2. 2. We administered intravenous, intramuscular, and intracerebroventricular CRH to nonhuman primates and measured plasma ACTH, beta endorphin, cortisol, GH and PRL responses to CRF. In addition, we determined the pharmacokinetic properties of I125 in these primates. 3. 3. We administered CRF as an intravenous bolus or as a continuous infusion to normal volunteers and as an intravenous bolus to patients with disorders of the hypothalamicpituitary-adrenal axis, such as Cushing's syndrome and adrenal insufficiency, and patients with endogenous depression and mild hypercortisolism, and assessed their plasma ACTH, cortisol, GH and PRL responses. In addition, we determined the pharmaco-kinetic properties of CRF in man by measuring CRF immunoreactivity in plasma. 4. 4. CRF given intravenously to primates or man is a slowly metabolized, long-acting, secretagogue of ACTH, beta-endorphin and cortisol. When given intracerebroventricularly to primates it stimulates the hypothalamic-pituitary-adrenal axis without escaping into the plasma and it is actively cleared in the CNS. It does not cross the blood brain barrier appreciably when given intravenously. CRF given to primates and men as an intravenous continuous infusion has only mild ACTH stimulating effects and this may be due to an intact cortisol negative feedback system. Finally, CRF causes characteristic plasma hormone responses in patients with Cushing's disease, adrenal insufficiency and depression.

Original languageEnglish (US)
Pages (from-to)349-359
Number of pages11
JournalProgress in Neuropsychopharmacology and Biological Psychiatry
Volume9
Issue number4
DOIs
Publication statusPublished - 1985
Externally publishedYes

    Fingerprint

Keywords

  • adrenal insufficiency
  • cortocotropin releasing factor (CRF)
  • Cushing's syndrome
  • depression
  • hypothalamic-pituitary-adrenal axis (HPA-axis)
  • primates

ASJC Scopus subject areas

  • Biological Psychiatry
  • Pharmacology

Cite this

Chrousos, G. P., Calabrese, J. R., Avgerinos, P., Kling, M. A., Rubinow, D., Oldfield, E. H., ... Gold, P. W. (1985). Corticotropin releasing factor: Basic studies and clinical applications. Progress in Neuropsychopharmacology and Biological Psychiatry, 9(4), 349-359. https://doi.org/10.1016/0278-5846(85)90187-3