Magnocellular Vasopressin and the Mechanism of “Glucocorticoid Escape”

Abstract

It is now widely accepted that magnocellular vasopressinergic neurons in the supraoptic and paraventricular nuclei participate in the control of adrenocorticotropin secretion by the anterior pituitary gland. However, it remains to be explored in further detail, when and how these multifunctional neurons are involved in the control of anterior pituitary function. This paper highlights the role of magnocellular vasopressin in the hypothalamic pituitary adrenocortical axis with special reference to escape from glucocorticoid feedback inhibition. The signaling mechanisms underlying glucocorticoid escape by pituitary corticotrope cells, as well as the wider physiologic and pathologic contexts in which escape is known to occur—namely strenuous exercise, and autoimmune inflammation will be considered. It is proposed that by inducing escape from glucocorticoid feedback inhibition at the pituitary level, magnocellular vasopressin is critically important for the anti-inflammatory, and immunosuppressant actions of endogenous corticosteroids.

The HPA Axis under Stress and Aging: Individual Vulnerability is Associated with Behavioral Patterns and Exposure Time

“…These neurons receive a large number of diverse neural signals from various parts of the brain, which contribute to the endocrine response to stress exposure. [ 31–34 ] CRH and AVP interact with specific receptors on corticotrophs of the anterior pituitary gland (CRH with CRHR1 and AVP with AVP1b, respectively) to induce ACTH secretion into the general circulation. [ 4,20,30–32 ] ACTH, after binding to type 2 melanocortin receptor in the adrenal cortex, activates a signaling cascade that usually leads to de novo biosynthesis and release of glucocorticoids (GCs).…”

“…[ 31–34 ] CRH and AVP interact with specific receptors on corticotrophs of the anterior pituitary gland (CRH with CRHR1 and AVP with AVP1b, respectively) to induce ACTH secretion into the general circulation. [ 4,20,30–32 ] ACTH, after binding to type 2 melanocortin receptor in the adrenal cortex, activates a signaling cascade that usually leads to de novo biosynthesis and release of glucocorticoids (GCs). [ 20,31,34,35 ] The main glucocorticoid in humans and non‐human primates is cortisol (CORT), and in most rodents, corticosterone.…”

“…Another important effect of GCs is the provision of inhibitory feedback at the level of hypothalamic neuroendocrine neurons, adenohypophysial corticotrophs, as well as higher brain centers involved in the regulation of neuroendocrine neurons (hippocampus, amygdala, and prefrontal cortex). [ 31,32,34,35 ]…”

“…Glucocorticoid genomic signaling involves the binding of glucocorticoids to two types of intracellular nuclear receptors, namely: mineralocorticoid receptor (MR), or type I receptor, and glucocorticoid receptor (GR), or type II receptor. [ 4,20,31,32,34 ] Glucocorticoids are characterized by 10 times higher affinity for MR compared to GR. This differential receptor affinity underlies the well‐known biphasic and inverted U‐shaped effects of glucocorticoids on many downstream signaling elements.…”

“…[ 20 ] MRs are predominantly expressed in the limbic structures of the brain, mainly in the hippocampus, as well as in the medial prefrontal cortex; in addition, MRs are found in the hypothalamus. [ 31,32,34 ] The functional (inhibitory) role of MR is proposed to proceed through tonic inhibitory projections, mediated by c‐aminobutyric acid (GABAergic) neurons, to the medial parvicellular neurons of the PVN, which control the secretion of ACTH via CRH and AVP. [ 34,35 ] GR, in turn, is widely expressed throughout the central nervous system, but predominates in the pituitary corticotrophs, PVN neurons, and the supraoptic nucleus of the hypothalamus.…”