Role of Pro-637 and Gln-642 in human glucocorticoid receptors and Ser-843 and Leu-848 in mineralocorticoid receptors in their differential responses to cortisol and aldosterone

2016 ◽  
Vol 159 ◽  
pp. 31-40 ◽  
Author(s):  
Orlando Mani ◽  
Lyubomir G. Nashev ◽  
Christopher Livelo ◽  
Michael E. Baker ◽  
Alex Odermatt
Keyword(s):  
Glucocorticoid Receptors ◽  
Mineralocorticoid Receptors ◽  
Differential Responses

scholarly journals Glucocorticoid receptors function in the pathophysiology of brain hypoxia

2019 ◽  
Vol 73 ◽  
pp. 838-849
Author(s):  
Jan Gregrowicz ◽  
Justyna Rogalska
Keyword(s):  
Glucocorticoid Receptors ◽  
Energy Deficit ◽  
Signalling Pathways ◽  
Main Role ◽  
Mineralocorticoid Receptors ◽  
Neuronal Fate ◽  
Penumbral Region ◽  
The Brain ◽  
Promote Cell Death

Glucocorticoid receptors are ligand-activated transcription factors, which play an important role in the brain, mainly in stress response regulation. There are two types of receptors for glucocorticosteroids: mineralocorticoid receptors (MR) with high-affinity for the ligands and glucocorticoid receptors (GR) with a tenfold lower affinity. Selective activation of the receptors during hypoxia may decide neuronal fate, especially in the hippocampus. Depending on the severity of hypoxia-induced damage, neurons undergo necrosis or apoptosis. In the penumbral region, where neurons die mainly through the process of apoptosis, selective GR activation increases excitotoxicity, interferes with apoptotic signalling pathways and causes energy deficit in the cells, all of which promote cell death. On the other hand, selective MR activation seems to be neuroprotective. It is suggested that the main role of MR in neuroprotection is to regulate the balance between anti- and proapoptotic proteins from bcl-2 family.

Alcohol Dependence Conceptualized as a Stress Disorder

2019 ◽  
pp. 198-220
Author(s):  
Leandro F. Vendruscolo ◽  
George F. Koob
Keyword(s):  
Prefrontal Cortex ◽  
Alcohol Use ◽  
Alcohol Dependence ◽  
Glucocorticoid Receptors ◽  
Critical Role ◽  
Emotional States ◽  
Brain Circuits ◽  
Negative Emotional State ◽  
Alcohol Alcohol

Alcohol use disorder is a chronically relapsing disorder that involves (1) compulsivity to seek and take alcohol, (2) difficulty in limiting alcohol intake, and (3) emergence of a negative emotional state (e.g., dysphoria, anxiety, irritability) in the absence of alcohol. Alcohol addiction encompasses a three-stage cycle that becomes more intense as alcohol use progresses: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. These stages engage neuroadaptations in brain circuits that involve the basal ganglia (reward hypofunction), extended amygdala (stress sensitization), and prefrontal cortex (executive function disorder). This chapter discusses key neuroadaptations in the hypothalamic and extrahypothalamic stress systems and the critical role of glucocorticoid receptors. These neuroadaptations contribute to negative emotional states that powerfully drive compulsive alcohol drinking and seeking. These changes in association with a disruption of prefrontal cortex function that lead to cognitive deficits and poor decision making contribute to the chronic relapsing nature of alcohol dependence.

scholarly journals Sexual dimorphic role of the glucocorticoid receptor in chronic muscle pain produced by early-life stress

2021 ◽  
Vol 17 ◽  
pp. 174480692110113
Author(s):  
Paul G Green ◽  
Pedro Alvarez ◽  
Jon D Levine
Keyword(s):  
Glucocorticoid Receptor ◽  
Adult Male ◽  
Life Stress ◽  
Early Life ◽  
Glucocorticoid Receptors ◽  
Early Life Stress ◽  
Nociceptive Threshold ◽  
Male And Female ◽  
Mechanical Nociceptive Threshold

Fibromyalgia and other chronic musculoskeletal pain syndromes are associated with stressful early life events, which can produce a persistent dysregulation in the hypothalamic-pituitary adrenal (HPA) stress axis function, associated with elevated plasm levels of corticosterone in adults. To determine the contribution of the HPA axis to persistent muscle hyperalgesia in adult rats that had experienced neonatal limited bedding (NLB), a form of early-life stress, we evaluated the role of glucocorticoid receptors on muscle nociceptors in adult NLB rats. In adult male and female NLB rats, mechanical nociceptive threshold in skeletal muscle was significantly lower than in adult control (neonatal standard bedding) rats. Furthermore, adult males and females that received exogenous corticosterone (via dams’ milk) during postnatal days 2–9, displayed a similar lowered mechanical nociceptive threshold. To test the hypothesis that persistent glucocorticoid receptor signaling in the adult contributes to muscle hyperalgesia in NLB rats, nociceptor expression of glucocorticoid receptor (GR) was attenuated by spinal intrathecal administration of an oligodeoxynucleotide (ODN) antisense to GR mRNA. In adult NLB rats, GR antisense markedly attenuated muscle hyperalgesia in males, but not in females. These findings indicate that increased corticosterone levels during a critical developmental period (postnatal days 2–9) produced by NLB stress induces chronic mechanical hyperalgesia in male and female rats that persists in adulthood, and that this chronic muscle hyperalgesia is mediated, at least in part, by persistent stimulation of glucocorticoid receptors on sensory neurons, in the adult male, but not female rat.

A role of glucocorticoid receptors in the guinea pig vestibular system

1999 ◽  
Vol 851 (1-2) ◽  
pp. 258-260 ◽  
Author(s):  
Hiroaki Shimogori ◽  
Hiroshi Yamashita ◽  
Tatsuo Watanabe ◽  
Shoji Nakamura
Keyword(s):  
Guinea Pig ◽  
Vestibular System ◽  
Glucocorticoid Receptors

Steroid hormone stimulation of Na+ transport in A6 cells is mediated via glucocorticoid receptors

1993 ◽  
Vol 264 (4) ◽  
pp. C875-C884 ◽  
Author(s):  
T. J. Schmidt ◽  
R. F. Husted ◽  
J. B. Stokes
Keyword(s):  
Cell Line ◽  
Glucocorticoid Receptors ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Mineralocorticoid Receptors ◽  
Na Transport ◽  
Receptor Complexes ◽  
Binding Forms ◽  
Mineralocorticoid Antagonists

The A6 cell line derived from the toad kidney forms polarized, highly differentiated epithelial monolayers in culture and has been utilized as an experimental model for studying regulation of transepithelial Na+ transport by aldosterone. In the present study we evaluated the specific role(s) of glucocorticoid and mineralocorticoid receptors in mediating this enhanced electrogenic Na+ transport, which was measured experimentally as an increase in short-circuit current (Isc). Our data demonstrate that specific glucocorticoid agonists (100 nM), including RU 28362 and RU 26988, elicit “mineralocorticoid-like” increases in Isc that are blocked by the glucocorticoid antagonist RU 38486 but are unaffected by mineralocorticoid antagonists including RU 28318 and RU 26752. The stimulatory effects of aldosterone (100 nM) were also blocked by RU 38486 and not by mineralocorticoid antagonists. These data extend earlier studies suggesting that in this cell line aldosterone mediates its physiological effects via binding with relatively low affinity (dissociation constant Kd congruent to 25-50 nM) to glucocorticoid receptors, despite the presence of apparently normal mineralocorticoid receptors. Our in vitro biochemical studies also demonstrate that A6 glucocorticoid receptor complexes can be thermally activated or transformed to DNA binding forms which exhibitaltered elution profiles from anion-exchange resins. Thus, based on several criteria, these amphibian glucocorticoid receptors appear very similar to classical mammalian receptors and are capable of mediating all of the stimulatory effects of aldosterone on net Na+ transport.

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