concept

glucocorticoid receptor

Also known as: GR, glucocorticoid receptors, nuclear glucocorticoid receptors

Facts (20)

Sources

Allostasis revisited: A perception, variation, and risk framework frontiersin.org Frontiers Sep 28, 2022 19 facts

claimBaker et al. (2013, 2015) state that the divergence of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) occurred around the time when bony fish and cartilaginous fish diverged.

claimComparative sequence analysis suggests that the glucocorticoid receptor (GR) rapidly diminished its hormone binding affinity after divergence, according to Carroll et al. (2011).

claimMany modern fish possess a third corticosteroid receptor subtype resulting from a more recent duplication of the glucocorticoid receptor (GR) gene.

claimThe difference in sensitivity between the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) allows for the segregation of function via signal amplitude, even in animals that employ only one corticosteroid, as noted by Carroll et al. (2008, 2011).

claimSapolsky et al. (2000) propose that mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) have categorical differences in function: MR effects permissive roles at low hormone concentrations, while GR effects suppressive, stimulating, or preparative roles at stress-induced concentrations.

claimEffects at physiological state level C are proposed to be mediated primarily through the low-affinity glucocorticoid receptor (GR).

referenceRecent evidence suggests that the heat-shock-related protein FKBP5 interacts with the glucocorticoid receptor (GR) to reduce its activity and could act as an ultra-short loop feedback signal, potentially enhancing the flexibility of the HPA axis in relation to environmental change.

referenceCarroll et al. (2011) analyzed mechanisms for the evolution of a derived function in the ancestral glucocorticoid receptor, published in PLoS Genetics.

referenceModern elasmobranchs possess both glucocorticoid and mineralocorticoid receptor types, utilize corticosterone and 1α-hydroxycorticosterone as potential agonists, and express 11β-hydroxysteroid dehydrogenase (HSD) type 2 enzymes, as noted by Carroll et al. (2008) and Baker et al. (2013).

claimNuclear mineralocorticoid receptors (MR) have high affinity but low capacity and become quickly saturated at lower glucocorticoid concentrations, whereas nuclear glucocorticoid receptors (GR) have a binding affinity an order of magnitude lower or more than MR and remain minimally occupied until hormone levels are elevated.

claimAlmost all modern vertebrates possess two types of corticosteroid receptors: mineralocorticoid receptors (MR) and glucocorticoid receptors (GR).

claimThe duplication and divergence of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) occurred approximately 450 million years ago, around the time bony fish and cartilaginous fish diverged.

claimMineralocorticoid receptors (MR) and glucocorticoid receptors (GR) are homologous, having diverged approximately 450 million years ago around the time bony fish and cartilaginous fish diverged (Baker et al., 2013, 2015).

referenceCarroll et al. (2011) suggest that the glucocorticoid receptor (GR) rapidly diminished its hormone binding affinity after evolutionary divergence.

referenceIn the model proposed by Landys et al. (2006), as plasma glucocorticoids increase, mineralocorticoid receptor (MR) occupancy reaches its peak and asymptotes, while glucocorticoid receptor (GR) occupancy occurs more slowly, representing physiological state levels B and C.

claimAs plasma glucocorticoids increase, mineralocorticoid receptor (MR) occupancy reaches its peak and asymptotes while the rate of glucocorticoid receptor (GR) occupancy occurs more slowly.

claimMineralocorticoid receptors (MR) bind both glucocorticoids and mineralocorticoids, whereas glucocorticoid receptors (GR) have lower affinity, bind exclusively to glucocorticoid hormones, and are nearly ubiquitously expressed (Baker et al., 2013).

claimThe distinction in binding affinity and function between mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) is broadly supportive of a threshold-based activation model.

claimIndividual responsiveness to perturbation resistance potential (PRP) varies and influences the activation of mineralocorticoid vs glucocorticoid-type receptors, hormone metabolizing enzymes, and other downstream factors in target tissues.

Mutual Shaping of Circadian Body-Wide Synchronization ... - Frontiers frontiersin.org Frontiers Jun 1, 2022 1 fact

claimGlucocorticoid receptors (GR) and mineralocorticoid receptors (MR) are functionally differentiated, with MR mainly participating in the baseline activity of glucocorticoids and GR regulating acute responses to stress.