Effects of a novel corticotropin-releasing-hormone receptor type I antagonist on human adrenal function
Willenberg HS, Bornstein SR, Hiroi N,
Path G, Goretzki PE, Scherbaum WA, Chrousos GP.
Diabetes Research Institute
at the University of Dusseldorf, Germany.
Mol Psychiatry 2000 Mar; 5(2):137-41


Corticotropin-releasing hormone (CRH) is the principal regulator of the hypothalamic-pituitary-adrenal (HPA) axis and an activator of the sympathoadrenal (SA) and systemic sympathetic (SS) systems. Mental disorders, including major depression and, more recently, Alzheimer's disease have been associated with dysregulation of the HPA axis and the SA/SS systems. Treatment of rats or monkeys with the novel CRH receptor type 1 (CRH-R1) antagonist antalarmin inhibits the HPA and/or the SA/SS axes. This is the first study to examine the potential direct effect of antalarmin on human adrenal function. Adrenocortical and adrenomedullary cells were characterized by double-immunohistochemistry with anti-17 alpha hydroxylase (cortical cells) and anti-chromogranin A (chromaffin cells). Expression of CRH, ACTH, CRH type I and type II receptor mRNA were analyzed by reverse-transcription (RT) PCR. Human adrenal cortical and/or chromaffin cells in co-culture were incubated with CRH, antalarmin, and both CRH and antalarmin in vitro. Exposure of these cells to corticotropin or vehicle medium served as positive and negative controls, respectively. Cortical and chromaffin tissues were interwoven in the human adrenals, and both in situ and in the co-culture system the endocrine cell types were in close cellular contact. ACTH, CRH, and CRH-R1 and CRH-R2 mRNAs were expressed in the human adrenal as determined by RT-PCR. CRH (10-8 M) led to a moderate increase of cortisol release (145.7 +/- 20.0%) from cortical and chromaffin adrenal cells in co-culture. This effect corresponded to 41.8% of the maximal increase induced by ACTH (10-8 M). The action of CRH was completely inhibited by antalarmin. CRH, ACTH, and both CRH-R1 and CRH-R2 mRNAs are expressed in the adult human adrenal gland. CRH stimulates cortisol production in cortical and chromaffin cell co-cultures. This effect is blocked by antalarmin, a selective CRH-R1 receptor antagonist, suggesting that CRH-R1 receptors are involved in an intraadrenal CRH/ACTH control system in humans.
Cushing's syndrome
Hippocampal remodelling
Glucocorticoids and mood
Antalarmin and the mouse
CRF-1 receptor antagonists
HPA axis, serotonin and suicide
Depression, opioids and the HPA
Antidepressants and new brain cells
The corticosteroid hypothesis of depression
An overactive immune system and depression
Stress, dynorphin, dysphoria and the kappa opioid system

and further reading

Future Opioids
BLTC Research
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Good Drug Guide

The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family