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The Corticotropin-Release Inhibitory Factor Hypothesis: A Review of the Evidence for the Existence of Inhibitory as Well as Stimulatory Hypophysiotropic Regulation of Adrenocorticotropin Secretion and Biosynthesis¹

Laboratory of Molecular Genetics and Development (D.E., I.K), Institute of Reproduction and Development, Monash Medical Centre, Clayton, Victoria, Australia 3168; and The Asher Center (E.R), Department of Psychiatry and Behavioral Sciences, Northwestern University Medical School, Chicago, Illinois 60611

I. Introduction

II. Hypothalamic Stimulation of ACTH Release and Biosynthesis

A. Corticotropin-releasing factor (CRF)

B. Arginine vasopressin (AVP)

C. The hypothalamic CRF and AVP neurons and their connections

D. Studies of the secretion of CRF and AVP into the hypophysial-portal circulation

E. Studies of the neural regulation of CRF and AVP secretion and biosynthesis

III. Hypothalamic Inhibition of ACTH Release and Biosynthesis

A. Historic studies

B. Effect of hypothalamo-pituitary disconnection in adult and fetal sheep

C. Effects of the opiate alkaloids and opioid peptides on the HPA axis

D. The role of the posterior pituitary in the regulation of corticotropic function

E. Hypothalamic ACTH release-inhibitory activity

F. Definition of corticotropin release inhibitory factor (CRIF)

IV. CRIF: A Consideration of Possible Candidates

A. Somatostatin (SST)

B. Dopamine

C. Atrial natriuretic peptide (ANP)

D. Prepro-TRH-(178–199)

E. Other substances

V. Future Directions