Glucocorticoid Receptors

Rousseau, Guy; Baxter, John D.

doi:10.1007/978-3-642-81265-1_3

Cited by 49 publications

(19 citation statements)

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“…Most of CORT's effects occur via intracellular receptors that, when activated, bind to DNA and alter gene transcription (Rousseau and Baxter, 1979). There are over 4000 glucocorticoid-specific response elements in DNA, which can lead to enhanced or suppressed transcription of more than 200 different genes (Reddy et al, 2009).…”

Section: Received 7 February 2014; Accepted 26 April 2014mentioning

confidence: 99%

“…However, knowing whether animals are successfully coping with stressors or suffering deleterious effects from an overactive HPA axis can be crucial for diagnosing the health of an individual animal. An approach that goes beyond quantification of plasma CORT concentrations may therefore be necessary.Most of CORT's effects occur via intracellular receptors that, when activated, bind to DNA and alter gene transcription (Rousseau and Baxter, 1979). There are over 4000 glucocorticoid-specific response elements in DNA, which can lead to enhanced or suppressed transcription of more than 200 different genes (Reddy et al, 2009).…”

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confidence: 99%

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Chronic stress alters concentrations of corticosterone receptors in a tissue-specific manner in wild house sparrows (Passer domesticus)

Lattin

Romero

2014

Journal of Experimental Biology

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The physiological stress response results in release of glucocorticoid hormones such as corticosterone (CORT). Whereas short-term activation of this response helps animals cope with environmental stressors, chronic activation can result in negative effects including metabolic dysregulation and reproductive failure. However, there is no consensus hormonal profile of a chronically stressed animal, suggesting that researchers may need to look beyond hormone titers to interpret the impacts of chronic stress. In this study, we brought wild house sparrows (Passer domesticus) into captivity. We then compared glucocorticoid and mineralocorticoid receptor concentrations in sparrows exposed either to a standardized chronic stress protocol (n=26) or to standard husbandry conditions (controls; n=20). We used radioligand binding assays to quantify receptors in whole brain, liver, kidneys, spleen, gonads, gastrocnemius and pectoralis muscle, omental and subcutaneous fat, and bib and back skin. In most tissues, CORT receptors did not differ between controls and stressed animals, although we found marginal increases in receptor density in kidney and testes in stressed birds at some time points. Only in pectoralis muscle was there a robust effect of chronic stress, with both receptor types higher in stressed animals. Increased pectoralis sensitivity to CORT with chronic stress may be part of the underlying mechanism for muscle wasting in animals administered exogenous CORT. Furthermore, the change in pectoralis was not paralleled by gastrocnemius receptors. This difference may help explain previous reports of a greater effect of CORT on pectoralis than on other muscle types, and indicate that birds use this muscle as a protein reserve. KEY WORDS: Hypothalamic-pituitary-adrenal axis, Glucocorticoids, Peripheral receptors, Bird INTRODUCTIONActivation of the hypothalamus-pituitary-adrenal (HPA) axis results in the release of glucocorticoid hormones (cortisol and/or corticosterone depending on the species, hereafter CORT). At baseline concentrations, CORT helps regulate metabolism, activity levels and feeding behavior; at the higher concentrations caused by a stressor, CORT is an essential component of the vertebrate stress response (Landys et al., 2006;Sapolsky et al., 2000). During the stress response, CORT helps animals mobilize energy stores, enhances certain immune components and promotes escape and selfmaintenance behaviors (Spencer et al., 2001;Wingfield and Kitaysky, 2002). RESEARCH ARTICLEDepartment of Biology, Tufts University, Medford, MA 02155, USA.*Author for correspondence (christine.lattin@tufts.edu) Received 7 February 2014; Accepted 26 April 2014However, sustained high levels of CORT due to frequent or prolonged stressors can result in a number of stress-related pathologies, including suppression of reproduction and the immune system, metabolic dysregulation and cognitive impairment (Dallman et al., 2003; de Kloet et al., 2005;Martin, 2009;Sapolsky et al., 2000). Chronic stress is thought to result once COR...

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Section: Received 7 February 2014; Accepted 26 April 2014mentioning

confidence: 99%

mentioning

confidence: 99%

Chronic stress alters concentrations of corticosterone receptors in a tissue-specific manner in wild house sparrows (Passer domesticus)

Lattin

Romero

2014

Journal of Experimental Biology

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“…1. While short-time competition assays with the tritiated forms of potent glucocorticoids such as dexamethasone are routinely used to determine the relative Kds of unlabeled steroids for receptors (17,18,21,26,(30)(31)(32), a half-time of 3-10 hrt for the dissociation of dexamethasone from receptors (34) requires that competition assays of 15-50 hr be used to obtain true equilibrium measurements. Thus, for steroids with slow dissociation rates, these competition assays largely reflect the varying association rates of steroid and receptor (21).…”

Section: Discussionmentioning

confidence: 99%

Unique long-acting antiglucocorticoid in whole and broken cell systems.

Simons¹,

Thompson²,

Johnson³

1980

Proc. Natl. Acad. Sci. U.S.A.

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The biological pro erties of cortisol 21-mesylate (CM), an alkylating derivative ofcortisol, were investigated in a line of rat hepatoma tissue culture (HTC) cells. CM appears to bind to glucocorticoid receptors in cell-free extracts because CM inhibits the specific binding of [3H]dexamethasone. However, in whole cells CM not only fails to induce the enzyme tyrosine aminotransferase (TyrATase) but also inhibits the induction of TyrATase by dexamethasone. Thus CM is an antiglucocorticoid. This is not caused by cell death, because CM is relatively nontoxic up to concentrations of 10 atM. The concentration of CM needed for half maximal inhibition of TyrATase induction is an order of magnitude lower than that predicted from the apparent cell-free affinity of CM for the glucocorticoid receptors of HTC cells, which suggests that the cell-free binding data does not reflect an equilibrium situation. In fact, the reactive a-keto mesylate group was intentionally incorporated into cortisol in hopes of obtaining a steroid capable of undergoing irreversible reactions. When HTC cells were preincubated with either CM or the reversible antiglucocorticoid progesterone and then washed to remove free steroid, only the CM-treated cells failed to show subsequent induction of TyrATase by dexamethasone. Furthermore, reincubation of HTC-cell cytosol with CM blocked t75% of the subsequent

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“…GR mediates the transcriptional effects of corticosteroids, like corticosterone (CORT) in rodents and cortisol in humans (Rousseau and Baxter, 1979). Mineralocorticoid receptors seem to play the role of a regulator of basal cortisol levels and GR comes into the picture when hormone levels are higher (Kolber et al, 2008).…”

Section: Transgenerational Behavioural Inheritance Involving Nuclear mentioning

confidence: 99%

Nuclear receptors in transgenerational epigenetic inheritance

Ozgyin

Erdős

Bojcsuk

et al. 2015

Progress in Biophysics and Molecular Biology

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Nuclear Receptors are ligand-activated transcription factors that translate information about the lipid environment into specific genetic programs, a property that renders them good candidates to be mediators of rapid adaptation changes of a species. Lipid-based morphogens, endocrine hormones, fatty acids and xenobiotics might act through this class of transcription factors making them regulators able to fine-tune physiological processes. Here we review the basic concepts and current knowledge on the process whereby small molecules act through nuclear receptors and contribute to transgenerational changes. Several molecules shown to cause transgenerational changes like phthalates, BPA, nicotine, tributylin bind and activate nuclear receptors like ERs, androgen receptors, glucocorticoid receptors or PPARγ. A specific subset of observations involving nuclear receptors has focused on the effects of environmental stress or maternal behaviour on the development of transgenerational traits. While these effects do not involve environmental ligands, they change the expression levels of Estrogen and glucocorticoid receptors of the second generation and consequently initiate an altered genetic program in the second generation. In this review we summarize the available literature about the role of nuclear receptors in transgenerational inheritance.

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Glucocorticoid Receptors

Cited by 49 publications

References 130 publications

Chronic stress alters concentrations of corticosterone receptors in a tissue-specific manner in wild house sparrows (Passer domesticus)

Chronic stress alters concentrations of corticosterone receptors in a tissue-specific manner in wild house sparrows (Passer domesticus)

Unique long-acting antiglucocorticoid in whole and broken cell systems.

Nuclear receptors in transgenerational epigenetic inheritance

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