Glucocorticoid regulation of peptide genes in neuroendocrine CRH neurons: A complexity beyond negative feedback

• Published in: Frontiers in neuroendocrinology Vol. 26; no. 3; pp. 109 - 130
• Main Author: Watts, Alan G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2005
• Subjects: Adrenocorticotropic Hormone - metabolism; Adrenocorticotropic Hormone - secretion; Amygdala; Animals; Circadian; Corticosterone; Corticotropin-Releasing Hormone - metabolism; Down-Regulation - physiology; Enkephalin; Feedback, Physiological - physiology; Glucocorticoids - physiology; Humans; Hypothalamus; Male; Neurons - metabolism; Neurons - secretion; Neurosecretory Systems - physiology; Paraventricular Hypothalamic Nucleus - cytology; Paraventricular Hypothalamic Nucleus - metabolism; Paraventricular nucleus; Peptide; Rat; Rats; Signal Transduction - physiology; Stress; Vasopressin; Rat; Amygdala; Corticosterone; Enkephalin; Paraventricular nucleus; Hypothalamus; Circadian; Peptide; Vasopressin; Stress
• ISSN: 0091-3022; 1095-6808
• DOI: 10.1016/j.yfrne.2005.09.001

This review will examine our current knowledge of a fundamental property of CRH neuroendocrine neurons: how the major endpoint of the HPA axis—adrenal glucocorticoids—interacts with the mechanisms controlling the expression of the genes that encode ACTH secretogogues. A great deal of work over the past 25 years has led to the notion that this question has an ostensibly simple answer: glucocorticoids inhibit peptide gene expression using “negative feedback” at the CRH neuron and elsewhere. However, closely examining how glucocorticoids act in different physiological circumstances reveals a much more complex set of answers, particularly if we consider how the processes that control peptide synthesis and release are coupled. Out of this examination emerges a more flexible and complex framework for examining the integrative mechanisms controlling the CRH neuron. Although we will mostly focus on the
Crh gene, relevant aspects of the vasopressin (
Avp) and pro-enkephalin (
pEnk) gene regulatory mechanisms will also be discussed.