Role of corticosteroid binding globulin in the fast actions of glucocorticoids on the brain

Moisan, Marie‐Pierre; Minni, Amandine; Dominguez, Gaëlle; Helbling, Jean‐Christophe; Foury, Aline; Henkous, Nadia; Dorey, Rodolphe; Béracochéa, Daniel

doi:10.1016/j.steroids.2013.10.013

Cited by 44 publications

(37 citation statements)

References 43 publications

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“…However, female rodent models are far less characterized than male rodents in biomedical research, including stress-associated despair-like behaviors (Kim et al, 2010;Wald and Wu, 2010;Zucker and Beery, 2010). CBG is involved in HPA axis sex differences and we have recently shown that its deficiency in males is associated with increased despairlike behavior and glucocorticoid hyposignaling (Minni et al, 2012;Moisan et al, 2014;Richard et al, 2010). In this study, we examined the role of CBG in emotional behaviors and HPA axis regulation in female mice, and compared them with those in males.…”

Section: Discussionmentioning

confidence: 99%

“…Since our previous studies have shown that low corticosterone levels were associated with the altered emotional behavior in Cbg k.o. males (Moisan et al, 2014;Richard et al, 2010), we have also characterized HPA axis regulation in female Cbg k.o. mice.…”

Section: Role Of Estrogens On Emotional Behavior In Wt and Cbg Ko Fmentioning

confidence: 99%

“…mice by infusing corticosterone directly into the hippocampus. The mechanisms explaining these effects involved an increased clearance but no difference in corticosterone production (Minni et al, 2012;Moisan et al, 2014;Richard et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Role of corticosteroid binding globulin in emotional reactivity sex differences in mice

Minni

Medeiros

Helbling

et al. 2014

Psychoneuroendocrinology

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Section: Discussionmentioning

confidence: 99%

Section: Role Of Estrogens On Emotional Behavior In Wt and Cbg Ko Fmentioning

confidence: 99%

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Role of corticosteroid binding globulin in emotional reactivity sex differences in mice

Minni

Medeiros

Helbling

et al. 2014

Psychoneuroendocrinology

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“…CBG does not simply limit free steroids in the plasma; it protects glucocorticoid from degradation and maintains a dynamic equilibrium of free and bound plasma glucocorticoid levels for tissue needs (101, 287). CBG-null transgenic mice have a significantly dampened corticosterone surge and display altered behavior in response to stress partially remediated by intrahippocampal infusion of corticosterone (308). DOC is also bound to CBG, however under normal circumstances, due to its lower total concentrations, relatively little free DOC is available receptor binding in comparison to cortisol, corticosterone or aldosterone (252).…”

Section: Mammalian Adrenocorticosteroids and Their Receptorsmentioning

confidence: 99%

The Multifaceted Mineralocorticoid Receptor

Gómez-Sánchez

2014

Comprehensive Physiology

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224

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The primary adrenal cortical steroid hormones, aldosterone, and the glucocorticoids cortisol and corticosterone, act through the structurally similar mineralocorticoid (MR) and glucocorticoid receptors (GRs). Aldosterone is crucial for fluid, electrolyte, and hemodynamic homeostasis and tissue repair; the significantly more abundant glucocorticoids are indispensable for energy homeostasis, appropriate responses to stress, and limiting inflammation. Steroid receptors initiate gene transcription for proteins that effect their actions as well as rapid non-genomic effects through classical cell signaling pathways. GR and MR are expressed in many tissues types, often in the same cells, where they interact at molecular and functional levels, at times in synergy, others in opposition. Thus the appropriate balance of MR and GR activation is crucial for homeostasis. MR has the same binding affinity for aldosterone, cortisol, and corticosterone. Glucocorticoids activate MR in most tissues at basal levels and GR at stress levels. Inactivation of cortisol and corticosterone by 11β-HSD2 allows aldosterone to activate MR within aldosterone target cells and limits activation of the GR. Under most conditions, 11β-HSD1 acts as a reductase and activates cortisol/corticosterone, amplifying circulating levels. 11β-HSD1 and MR antagonists mitigate inappropriate activation of MR under conditions of oxidative stress that contributes to the pathophysiology of the cardiometabolic syndrome; however, MR antagonists decrease normal MR/GR functional interactions, a particular concern for neurons mediating cognition, memory, and affect.

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“…Bár a CBG szintje akut stresszben drámaian nem változik, nemcsak passzív résztvevője a folyamatnak. CBG génkiütött (KO) egereken végzett kí-sérletek azt bizonyítják, hogy a GC-k gyors hatásaihoz (például memória) szükség van a kötőfehérjére, ami megvédi a GC-ket a lebontástól [12]. A CBG a szexuálszteroidok erőteljes befolyása alatt áll: szintjét az öszt-rogének megemelik, és a progeszteron pedig kötődni képes hozzá.…”

Section: Farmakokinetikaunclassified

Szteroidok: A glükokortikoidok élettani és gyógyszertani hatásai

Zelena

Makara

2015

Orvosi Hetilap

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Az orvosi gyakorlatban kiterjedten alkalmazzák a glükokortikoidokat elsősorban az immunrendszer működésének elnyomása, a gyulladásos folyamatok gátlása céljából. Másrészről a nevüket is adó Selye szerint az endogén molekulák az elsődleges megvalósítói a kihívásokhoz való alkalmazkodásnak, a stresszreakciónak. A glükokortikoidokat az 1940-es években szintetizálták, és azóta számtalan adat látott napvilágot a termelődésükről (számos szervben lokálisan is), szállításukról (elsősorban a kortizolkötő globulinnal) és receptoraikról (magreceptor és nem genomiális hatások). Bár szabályozásuk elsődlegesen a hypothalamus-hipofízis-mellékvese tengely adrenokortikotropin hormonjának befolyá-sa alatt áll, de számos egyéb molekula (elsősorban katecholaminok a mellékvesevelőből) is fokozhatja az elválasztásu-kat. Fő szerepük permisszív, azaz a glükokortikoidok számos egyéb molekula hatásának kifejtéséhez elengedhetetlenek (például katecholaminok). Így nagyon szerteágazó befolyással bírnak a metabolizmustól a cardiovascularis hatásokon át a csontanyagcseréig, még a központi idegrendszeri működések szabályozására is kihatással vannak. A metabolikus szindróma kapcsán is előtérbe kerültek. Kiterjedt terápiás alkalmazásukat a mellékhatások problémássá teszik, amelyek kivédésére például az anabolikus dehidroepiandroszteron egyidejű adagolása is szóba kerülhet. Orv. Hetil., 2015, 156(35), 1415-1425.Kulcsszavak: glükokortikoidok, receptorok, farmakokinetika, szerep, patofi ziológia Steroids: The physiological and pharmacological effects of glucocorticoidsGlucocorticoids are widely used in medical practice mainly for suppression of the immune system. According to Selye -who named them -the endogenous molecules are very important for the adaptation to challenges, stress. They were synthesized in the 1940s. Since then numerous data have been published about their production (also locally in several organs), transportation (primarily cortisol-binding globulin) and receptors (nuclear and non-genomic effects). Although glucocorticoids are primarily under the control of the hypothalamo-pituitary-adrenocortical axis, several other molecules (especially catecholamines) may also increase their secretion. Their permissive infl uences are dominant, thereby they are indispensable for the effect of numerous other molecules. Thus, glucocorticoids have very diverse infl uence from metabolism through cardiovascular effect to bone-metabolism, affecting even the central nervous system. They are also important in metabolic syndrome. Their extensive therapeutic usage are limited by side-effects, which could be diminished -among others -with concomitant usage of the anabolic dehydroepiandrosterone. Rövidítések ACTH = adrenokortikotropin; CAH = congenitalis adrenalis hyperplasia; CBG = cortisol binding globulin; COX = ciklooxigenáz; CRH = kortikotropinelválasztást serkentő hormon; DHEA = dehidroepiandroszteron; DHEAS = dehidroepiandroszteron-szulfát; DOC = deoxi-kortikoszteron; GC = glüko-kortikoid; GR = glükokortikoidreceptor; HHM = hypothalamus-hipofízis-...

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Role of corticosteroid binding globulin in the fast actions of glucocorticoids on the brain

Cited by 44 publications

References 43 publications

Role of corticosteroid binding globulin in emotional reactivity sex differences in mice

Role of corticosteroid binding globulin in emotional reactivity sex differences in mice

The Multifaceted Mineralocorticoid Receptor

Szteroidok: A glükokortikoidok élettani és gyógyszertani hatásai

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