Placental mRNA levels of genes regulating fetal glucocorticoid and neurotransmitter exposure correlate with birth size, but not in very severely obese pregnancy (original) (raw)
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Endocrine Reviews, 2000
The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated. In this review, we consider recent findings regarding GC action and, based on them, generate criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stressresponse or, as an additional category, is preparative for a subsequent stressor. We apply these GC actions to the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology. We find that GC actions fall into markedly different categories, depending on the physiological endpoint in question, with evidence for mediating effects in some cases, and suppressive or preparative in others. We then attempt to assimilate these heterogeneous GC actions into a physiological whole. (Endocrine Reviews 21: 55-89, 2000) I. The Decline and Modern Revision of Glucocorticoid Physiology II. Definition of Terms, and Criteria for Analyzing the Role of GCs in the Stress Response A. The prototypical stress response B. Definitions of the classes of GC actions C. Criteria for analyzing the role of GCs in the stress response III. GC Actions in the Context of These Criteria A. Cardiovascular effects B. Fluid volume and hemorrhage C. Immunity and inflammation D. Metabolism E. Neurobiological effects F. Reproductive physiology IV. An Integration A. The logic of the heterogeneity of categories of glucocorticoid actions B. An appreciation of permissive glucocorticoid actions C. The relevance of preparative actions in an ethological context V. Molecular Mechanisms Underlying Actions of GCs in Stress A. Permissive and suppressive actions: MRs or GRs? B. Role of 11-hydroxysteroid dehydrogenases C. General mechanisms of transcriptional activation and repression by GCs D. GC actions on immunity and inflammation E. Metabolic GC actions F. Studies with transgenic mice VI. Conclusions I. The Decline and Modern Revision of Glucocorticoid Physiology
2022
Repeated acute stress (RASt) is known to be associated with gastrointestinal dysfunctions. However, mechanisms underlying these effects are not fully understood. While glucocorticoids are clearly identified as hormones of stress, their implication, and those of their specific glucocorticoid receptors (GR), in RASt induced gut dysfunctions remain unclear. The aim of our study was to evaluate the involvement of GR on RASt induced changes in gut motility, particularly through the enteric nervous system (ENS). Using a murine water avoidance stress model, we characterized the impact of RASt upon ENS phenotype and colonic motility. Next, the expression of GR onto the ENS and their functional impact upon RASt induced changes in ENS phenotype and motor response were evaluated. We showed that the GR was expressed in myenteric neurons in the distal colon under basal condition, and that RASt enhanced its nuclear translocation. RASt increased the proportion of ChAT-IR neurons, acetylcholine tis...
Role of Glucocorticoids in Tuning Hindbrain Stress Integration
2010
The nucleus of the solitary tract (NTS) is a critical integrative site for coordination of autonomic and endocrine stress responses. Stress-excitatory signals from the NTS are communicated by both cathecholaminergic (norepinephrine (NE), epinephrine(E)) and non-catecholaminergic (e.g., glucagon-like peptide-1 (GLP-1) neurons). Recent studies suggest that outputs of the NE/E and GLP-1 neurons of the NTS are selectively engaged during acute stress. This study was designed to test mechanisms of chronic stress integration in the PVN, focusing on the role of glucocorticoids. Our data indicate that chronic variable stress (CVS) causes down-regulation of preproglucagon (GLP-1 precursor) mRNA in the NTS and reduction of GLP-1 innervation to the paraventricular nucleus of the hypothalamus. Glucocorticoids were necessary for PPG reduction in CVS animals, and were sufficient to lower PPG mRNA in otherwise unstressed animals. The data are consistent with a glucocorticoid-mediated withdrawal of GLP-1 in key stress circuits. In contrast, expression of tyrosine hydroxylase (TH) mRNA, the rate limiting enzyme in catecholamine synthesis, was increased by stress in a glucocorticoid-independent manner. These suggest differential roles of ascending catecholamine and GLP-1 systems in chronic stress, with withdrawal of GLP-1 involved in stress adaptation, and enhanced NE/E capacity responsible for facilitation of responses to novel stress experiences.
Early-life stress induces visceral hypersensitivity in mice
Neuroscience letters, 2012
Early-life stress is a risk factor for irritable bowel syndrome (IBS), a common and debilitating functional gastrointestinal disorder that is often co-morbid with stress-related psychiatric disorders. In the rat, maternal separation (MS) stress has been shown to induce visceral hypersensitivity in adulthood and thus has become a useful model of IBS. However, development of mouse models of maternal separation has been difficult. Given the advent of transgenic mouse technology, such models would be useful to further our understanding of the pathophysiology of IBS and to develop new pharmacological treatments. Thus, the present study aimed to develop a mouse model of MS stress-induced visceral hyperalgesia as measured using manometric recordings of colorectal distension (CRD). Moreover, since the GABA(B) receptor has been reported to play a role in pain processes, we also assessed its role in visceral nociception using novel GABA(B(1b)) receptor subunit knockout mice. CRD was performed...
Neurogastroenterology & Motility, 2012
Background-Stress worsens abdominal pain experienced by patients with irritable bowel syndrome (IBS), a chronic disorder of unknown origin with comorbid anxiety. We have previously demonstrated colonic hypersensitivity in Wistar-Kyoto rats (WKYs), a high-anxiety strain, that models abdominal pain in IBS. In low-anxiety rats, we have demonstrated that the central nucleus of the amygdala (CeA) regulates colonic hypersensitivity and anxiety induced by selective activation of either glucocorticoid receptors (GR) or mineralocorticoid receptors (MR), which is also mediated by the corticotropin releasing factor (CRF) type-1 receptor. The goal of the present study was to test the hypothesis that the CeA through GR, MR and/or CRF-1R regulates colonic hypersensitivity in WKYs. Methods-One series of WKYs had micropellets of a GR antagonist, an MR antagonist or cholesterol (control) stereotaxically implanted onto the CeA. Another series were infused in the CeA with CRF-1R antagonist or vehicle. Colonic sensitivity was measured as a visceromotor response (VMR) to graded colorectal distension (CRD). Key Results-The exaggerated VMR to graded CRD in WKYs was unaffected by GR or MR antagonism in the CeA. In contrast, direct CeA infusion of CRF-1R antagonist significantly inhibited the VMR to CRD at noxious distension pressures. Conclusions & Inferences-Stress-hormones in the CeA regulate colonic hypersensitivity in the rat through strain-dependent parallel pathways. The colonic hypersensitivity in WKYs is mediated by a CRF-1R mechanism in the CeA, independent of GR and MR. These complementary pathways suggest multiple etiologies whereby stress hormones in the CeA may regulate abdominal pain in IBS patients.
Neural regulation of the stress response: Glucocorticoid feedback mechanisms
2012
The mammalian stress response is an integrated physiological and psychological reaction to real or perceived adversity. Glucocorticoids are an important component of this response, acting to redistribute energy resources to both optimize survival in the face of challenge and to restore homeostasis after the immediate challenge has subsided. Release of glucocorticoids is mediated by the hypothalamo-pituitary-adrenal (HPA) axis, driven by a neural signal originating in the paraventricular nucleus (PVN). Stress levels of glucocorticoids bind to glucocorticoid receptors in multiple body compartments, including the brain, and consequently have wide-reaching actions. For this reason, glucocorticoids serve a vital function in negative feedback inhibition of their own secretion. Negative feedback inhibition is mediated by a diverse collection of mechanisms, including fast, non-genomic feedback at the level of the PVN, stress-shut-off at the level of the limbic system, and attenuation of ascending excitatory input through destabilization of mRNAs encoding neuropeptide drivers of the HPA axis. In addition, there is evidence that glucocorticoids participate in stress activation via feed-forward mechanisms at the level of the amygdala. Feedback deficits are associated with numerous disease states, underscoring the necessity for adequate control of glucocorticoid homeostasis. Thus, rather than having a single, defined feedback 'switch', control of the stress response requires a wide-reaching feedback 'network' that coordinates HPA activity to suit the overall needs of multiple body systems.
Experimental neurology, 2015
Chronic stress alters the hypothalamic-pituitary-adrenal (HPA) axis and enhances visceral and somatosensory pain perception. It is unresolved whether chronic stress has distinct effects on visceral and somatosensory pain regulatory pathways. Previous studies reported that stress-induced visceral hyperalgesia is associated with reciprocal alterations of endovanilloid and endocannabinoid pain pathways in DRG neurons innervating the pelvic viscera. In this study, we compared somatosensory and visceral hyperalgesia with respect to differential responses of peripheral pain regulatory pathways in a rat model of chronic, intermittent stress. We found that chronic stress induced reciprocal changes in the endocannabinoid 2-AG (increased) and endocannabinoid degradation enzymes COX-2 and FAAH (decreased), associated with down-regulation of CB1 and up-regulation of TRPV1 receptors in L6-S2 DRG but not L4-L5 DRG neurons. In contrast, sodium channels Nav1.7 and Nav1.8 were up-regulated in L4-L5 ...
Scientific Reports, 2019
The hypothalamic-pituitary-adrenal (HPA) axis regulates responses to internal and external stressors. Many patients diagnosed with conditions such as depression or anxiety also have hyperactivity of the HPA axis. Hyper-stimulation of the HPA axis results in sustained elevated levels of glucocorticoids which impair neuronal function and can ultimately result in a psychiatric disorder. Studies investigating Glucocorticoid Receptor (GR/NR3C1) in the brain have primarily focused on the forebrain, however in recent years, the hindbrain has become a region of interest for research into the development of anxiety and depression, though the role of GR signalling in the hindbrain remains poorly characterised. To determine the role of glucocorticoid signalling in the hindbrain we have developed a novel mouse model that specifically ablates hindbrain GR to ascertain its role in behaviour, HPA-axis regulation and adrenal structure. Our study highlights that ablation of GR in the hindbrain resul...