Brain mineralocorticoid receptors (MR) mediate effects of glucocorticoid hormones in stress adaptation, as well as the effects of aldosterone itself in relation to salt homeostasis. Brain stem MRs... Show moreBrain mineralocorticoid receptors (MR) mediate effects of glucocorticoid hormones in stress adaptation, as well as the effects of aldosterone itself in relation to salt homeostasis. Brain stem MRs respond to aldosterone, whereas forebrain MRs mediate rapid and delayed glucocorticoid effects in conjunction with the glucocorticoid receptor (GR). MR-mediated effects depend on age, gender, genetic variations, and environmental influences. Disturbed MR activity through chronic stress, certain (endocrine) diseases or during glucocorticoid therapy can cause deleterious effects on affective state, cognitive and behavioural function in susceptible individuals. Considering the important role MR plays in cognition and emotional function in health and disease, MR modulation by pharmacological intervention could relieve stress- and endocrine-related symptoms. Here, we discuss recent pharmacological interventions in the clinic and genetic developments in the molecular underpinnings of MR signalling. Further understanding of MR-dependent pathways may help to improve psychiatric symptoms in a diversity of settings. Show less
Adrenal glucocorticoid hormones are crucial for maintenance of homeostasis and adaptation to stress. They act via the mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs)-members of... Show moreAdrenal glucocorticoid hormones are crucial for maintenance of homeostasis and adaptation to stress. They act via the mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs)-members of the family of nuclear receptors. MRs and GRs can mediate distinct, sometimes opposite, effects of glucocorticoids. Both receptor types can mediate nongenomic steroid effects, but they are best understood as ligand-activated transcription factors. MR and GR protein structure is similar; the receptors can form heterodimers on the DNA at glucocorticoid response elements (GREs), and they share a number of target genes. The transcriptional basis for opposite effects on cellular physiology remains largely unknown, in particular with respect to MR-selective gene transcription. In this review, we discuss proven and potential mechanisms of transcriptional specificity for MRs and GRs. These include unique GR binding to "negative GREs," direct binding to other transcription factors, and binding to specific DNA sequences in conjunction with other transcription factors, as is the case for MRs and NeuroD proteins in the brain. MR- and GR-specific effects may also depend on specific interactions with transcriptional coregulators, downstream mediators of transcriptional receptor activity. Current data suggest that the relative importance of these mechanisms depends on the tissue and physiological context. Insight into these processes may not only allow a better understanding of homeostatic regulation but also the development of drugs that target specific aspects of disease. Copyright (C) 2019 Endocrine Society Show less
To adequately respond to crises, adaptive governance is crucial, but sometimes institutional adaptation is constrained, even when a society is faced with acute hazards. We hypothesize that economic... Show moreTo adequately respond to crises, adaptive governance is crucial, but sometimes institutional adaptation is constrained, even when a society is faced with acute hazards. We hypothesize that economic inequality, defined as unequal ownership of wealth and access to resources, crucially interacts with the way institutions function and are adapted or not. Because the time span for societal responses may be lengthy, we use the historical record as a laboratory to test our hypothesis. In doing so, we focus on floods and water management infrastructure. The test area is one where flood hazards were very evident—the Low Countries (present-day Netherlands and Belgium) in the premodern period (1300–1800)—and we employ comparative analysis of three regions within this geographical area. We draw two conclusions: first, both equitable and inequitable societies can demonstrate resilience in the face of floods, but only if the institutions employed to deal with the hazard are suited to the distributive context. Institutions must change parallel to any changes in inequality. Second, we show that institutional adaptation was not inevitable, but also sometimes failed to occur. Institutional adaptation was never inevitably triggered by stimulus of a hazard, but dependent on socio-political context. Even when vital for the community under threat, adaptation only tended to occur when the vested interests of those with wealth, resources, and power were directly hit. Show less
Engelhart, D.; Pasma, J.H.; Schouten, A.C.; Aarts, R.G.K.M.; Meskers, C.G.M.; Maier, A.B.; Kooij, H. van der 2016
