30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor null mice: informing cell-type-specific roles
The mineralocorticoid receptor (MR) mediates the actions of two important adrenal corticosteroid hormones, aldosterone and cortisol. The cell signalling roles of the MR in vivo have expanded enormously since the cloning of human MR gene 30 years ago and the first MR gene knockout in mice nearly 20 years ago. Complete ablation of the MR revealed important roles postnatally for regulation of kidney epithelial functions, with MR-null mice dying 1–2 weeks postnatally from renal salt wasting and hyperkalaemia, with elevated plasma renin and aldosterone. Generation of tissue-selective MR-deficient mice using Cre recombinas...
Source: Journal of Endocrinology - June 20, 2017 Category: Endocrinology Authors: Cole, T. J., Young, M. J. Tags: Thematic Review Source Type: research
30 YEARS OF THE MINERALOCORTICOID RECEPTOR: The role of the mineralocorticoid receptor in the vasculature
Since the mineralocorticoid receptor (MR) was cloned 30 years ago, it has become clear that MR is expressed in extra-renal tissues, including the cardiovascular system, where it is expressed in all cells of the vasculature. Understanding the role of MR in the vasculature has been of particular interest as clinical trials show that MR antagonism improves cardiovascular outcomes out of proportion to changes in blood pressure. The last 30 years of research have demonstrated that MR is a functional hormone-activated transcription factor in vascular smooth muscle cells and endothelial cells. This review summarizes advances in o...
Source: Journal of Endocrinology - June 20, 2017 Category: Endocrinology Authors: DuPont, J. J., Jaffe, I. Z. Tags: Thematic Review Source Type: research
Endocrine targets of hypoxia-inducible factors
Endocrine is an important and tightly regulated system for maintaining body homeostasis. Endocrine glands produce hormones, which are released into blood stream to guide the target cells responding to all sorts of stimulations. For maintaining body homeostasis, the secretion and activity of a particular hormone needs to be adjusted in responding to environmental challenges such as changes in nutritional status or chronic stress. Hypoxia, a status caused by reduced oxygen availability or imbalance of oxygen consumption/supply in an organ or within a cell, is a stress that affects many physiological and pathological processe...
Source: Journal of Endocrinology - June 20, 2017 Category: Endocrinology Authors: Lee, H.-C., Tsai, S.-J. Tags: Review Source Type: research
30 YEARS OF THE MINERALOCORTICOID RECEPTOR: The brain mineralocorticoid receptor: a saga in three episodes
In 1968, Bruce McEwen discovered that 3H-corticosterone administered to adrenalectomised rats is retained in neurons of hippocampus rather than those of hypothalamus. This discovery signalled the expansion of endocrinology into the science of higher brain regions. With this in mind, our contribution highlights the saga of the brain mineralocorticoid receptor (MR) in three episodes. First, the precloning era dominated by the conundrum of two types of corticosterone-binding receptors in the brain, which led to the identification of the high-affinity corticosterone receptor as the ‘promiscuous’ MR cloned in 1987 b...
Source: Journal of Endocrinology - June 20, 2017 Category: Endocrinology Authors: Joels, M., de Kloet, E. R. Tags: Thematic Review Source Type: research
Aging human body: changes in bone, muscle and body fat with consequent changes in nutrient intake
Aging affects almost all physiological processes, but changes in body composition and body phenotype are most observable. In this review, we focus on these changes, including loss of bone and muscle and increase in body fat or redistribution of the latter, possibly leading to osteosarcopenic obesity syndrome. We also address low-grade chronic inflammation, prevalent in aging adults and a cause of many disorders including those associated with body composition. Changes in dietary intake and nutritional requirements of older individuals, that all may lead to some disturbances on tissue and organ levels, are discussed as well...
Source: Journal of Endocrinology - June 20, 2017 Category: Endocrinology Authors: JafariNasabian, P., Inglis, J. E., Reilly, W., Kelly, O. J., Ilich, J. Z. Tags: Review Source Type: research
30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor and NaCl transport mechanisms in the renal distal nephron
A key role of aldosterone and mineralocorticoid receptor is to regulate fluid volume and K+ homeostasis in the body by acting on the renal distal nephron. Global responses of the kidney to elevated aldosterone levels are determined by the coordinate action of different constituent tubule cells, including principal cells, intercalated cells and distal convoluted tubule cells. Recent studies on genetic mutations causing aldosterone overproduction have identified the molecules involved in aldosterone biosynthesis in the adrenal gland, and there is also increasing evidence for mechanisms and signaling pathways regulating the b...
Source: Journal of Endocrinology - June 20, 2017 Category: Endocrinology Authors: Shibata, S. Tags: Thematic Review Source Type: research
30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Coregulators as mediators of mineralocorticoid receptor signalling diversity
The cloning of the mineralocorticoid receptor (MR) 30 years ago was the start of a new era of research into the regulatory processes of MR signalling at target genes in the distal nephron, and subsequently in many other tissues. Nuclear receptor (NR) signalling is modified by interactions with coregulatory proteins that serve to enhance or inhibit the gene transcriptional responses. Over 400 coregulatory proteins have been described for the NR super family, many with functional roles in signalling, cellular function, physiology and pathophysiology. Relatively few coregulators have however been described for the MR although...
Source: Journal of Endocrinology - June 20, 2017 Category: Endocrinology Authors: Fuller, P. J., Yang, J., Young, M. J. Tags: Thematic Review Source Type: research
30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor activation and specificity-conferring mechanisms: a brief history
(Source: Journal of Endocrinology)
Source: Journal of Endocrinology - June 20, 2017 Category: Endocrinology Authors: Funder, J. Tags: Thematic Review Source Type: research
30 YEARS OF THE MINERALOCORTICOID RECEPTOR: The scientific impact of cloning the mineralocorticoid receptor: 30 years on
(Source: Journal of Endocrinology)
Source: Journal of Endocrinology - June 20, 2017 Category: Endocrinology Authors: Funder, J. W., Zennaro, M.-C. Tags: Editorials Source Type: research
30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Evolution of the mineralocorticoid receptor: sequence, structure and function
The mineralocorticoid receptor (MR) is descended from a corticoid receptor (CR), which has descendants in lamprey and hagfish, cyclostomes (jawless fish), a taxon that evolved at the base of the vertebrate line. A distinct MR and GR first appear in cartilaginous fishes (Chondrichthyes), such as sharks, skates, rays and chimeras. Skate MR has a strong response to corticosteroids that are mineralocorticoids and glucocorticoids in humans. The half-maximal responses (EC50s) for skate MR for the mineralocorticoids aldosterone and 11-deoxycorticosterone are 0.07 nM and 0.03 nM, respectively. EC50s for the glucocorticoids cortiso...
Source: Journal of Endocrinology - June 20, 2017 Category: Endocrinology Authors: Baker, M. E., Katsu, Y. Tags: Thematic Review Source Type: research
30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Short reflections on the discovery of the mineralocorticoid receptor
(Source: Journal of Endocrinology)
Source: Journal of Endocrinology - June 20, 2017 Category: Endocrinology Authors: Evans, R. M. Tags: Editorials Source Type: research
The interfaces between vitamin D, sleep and pain
The role of vitamin D in osteomineral metabolism is well known. Several studies have suggested its action on different biological mechanisms, such as nociceptive sensitivity and sleep–wake cycle modulation. Sleep is an important biological process regulated by different regions of the central nervous system, mainly the hypothalamus, in combination with several neurotransmitters. Pain, which can be classified as nociceptive, neuropathic and psychological, is regulated by both the central and peripheral nervous systems. In the peripheral nervous system, the immune system participates in the inflammatory process that co...
Source: Journal of Endocrinology - June 2, 2017 Category: Endocrinology Authors: de Oliveira, D. L., Hirotsu, C., Tufik, S., Andersen, M. L. Tags: Review Source Type: research
Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones
Fatty liver can be diet, endocrine, drug, virus or genetically induced. Independent of cause, hepatic lipid accumulation promotes systemic metabolic dysfunction. By acting as peroxisome proliferator-activated receptor (PPAR) ligands, hepatic non-esterified fatty acids upregulate expression of gluconeogenic, beta-oxidative, lipogenic and ketogenic genes, promoting hyperglycemia, hyperlipidemia and ketosis. The typical hormonal environment in fatty liver disease consists of hyperinsulinemia, hyperglucagonemia, hypercortisolemia, growth hormone deficiency and elevated sympathetic tone. These endocrine and metabolic changes fu...
Source: Journal of Endocrinology - June 2, 2017 Category: Endocrinology Authors: Geisler, C. E., Renquist, B. J. Tags: Review Source Type: research
Thermal imprinting modifies adult stress and innate immune responsiveness in the teleost sea bream
The impact of thermal imprinting on the plasticity of the hypothalamic–pituitary–interrenal (HPI) axis and stress response in an adult ectotherm, the gilthead sea bream (Sparus aurata, L.), during its development was assessed. Fish were reared under 4 thermal regimes, and the resulting adults exposed to acute confinement stress and plasma cortisol levels and genes of the HPI axis were monitored. Changes in immune function, a common result of stress, were also evaluated using histomorphometric measurements of melanomacrophages centers (MMCs) in the head kidney and by monitoring macrophage-related transcripts. Th...
Source: Journal of Endocrinology - May 31, 2017 Category: Endocrinology Authors: Mateus, A. P., Costa, R. A., Cardoso, J. C. R., Andree, K. B., Estevez, A., Gisbert, E., Power, D. M. Tags: Research Source Type: research
The immunoproteasome is induced by cytokines and regulates apoptosis in human islets
In addition to degrading misfolded and damaged proteins, the proteasome regulates the fate of cells in response to stress. The role of the proteasome in pro-inflammatory cytokine-induced human beta-cell apoptosis is unknown. Using INS-1, INS-1E and human islets exposed to combinations of IFN, IL-1β and TNFα with or without addition of small molecules, we assessed the role of the immunoproteasome in pancreatic beta-cell demise. Here, we show that cytokines induce the expression and activity of the immuno-proteasome in INS-1E cells and human islets. Cytokine-induced expression of immuno-proteasome subunits, but no...
Source: Journal of Endocrinology - May 31, 2017 Category: Endocrinology Authors: Lundh, M., Bugliani, M., Dahlby, T., Chou, D. H.-C., Wagner, B., Ghiasi, S. M., De Tata, V., Chen, Z., Lund, M. N., Davies, M. J., Marchetti, P., Mandrup-Poulsen, T. Tags: Research Source Type: research
