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Mineralocorticoid

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https://www.readbyqxmd.com/read/28533421/mineralocorticoid-receptor-activation-and-specificity-conferring-mechanisms-a-short-history
#1
John W Funder
The mineralocorticoid receptor (henceforth MR) was first characterized 45 years ago (Funder 1972, Rousseau 1972), a decade and a half before its successful cloning (Arriza 1987) to which this issue of the Journal is dedicated. Aldosterone had been isolated and characterized 20 years before the MR: its initial name was electrocortin, reflecting its ability to promote electrolyte transport across epithelial membranes, rapidly changed to its familiar, current name aldosterone. What prompted the change was the finding of a unique aldehyde group at carbon18 of the steroid molecule, the physiological significance of which only became clear many years later (Funder 1988, Edwards 1988)...
May 22, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28533238/posaconazole-induced-hypertension-and-hypokalemia-in-vivo-11%C3%AE-hydroxysteroid-dehydrogenase-inhibition
#2
George R Thompson, Diana Chang, Rebecca R Wittenberg, Ian McHardy, Alison Semrad
We describe a case of apparent mineralocorticoid excess (AME) secondary to posaconazole and suggest the biochemical mechanism. Clinical and laboratory investigation confirmed 11β-hydroxysteroid dehydrogenase inhibition and withholding therapy led to a resolution of all clinical and laboratory abnormalities. A lower dose of posaconazole was later restarted and avoided recurrence of this syndrome. Additional studies are necessary to determine the frequency of posaconazole induced AME and whether other azole antifungals can be associated with this phenomenon...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533088/a-ubiquitin-proteasome-inhibitor-bortezomib-suppresses-the-expression-of-cyp11b2-a-key-enzyme-of-aldosterone-synthesis-as-revealed-by-chemical-screening
#3
Ryo Ito, Ikuko Sato, Tadayuki Tsujita, Atsushi Yokoyama, Akira Sugawara
CYP11B2 is a key enzyme involved in the synthesis of the mineralocorticoid aldosterone. CYP11B2 expression in the adrenal glands is controlled by the renin-angiotensin system (RAS), and plays an important role in the maintenance of electrolyte metabolism in higher organisms. Abnormal overexpression of CYP11B2 results in the disruption of mineral balance and can lead to hypertension. Though the molecular mechanism of the regulation of CYP11B2 expression has remained elusive, we hypothesize that compounds that prevent CYP11B2 expression could represent a novel class of antihypertensive drugs...
May 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28523794/mineralocorticoid-receptor-associates-with-pro-inflammatory-bias-in-hippocampus-of-spontaneously-hypertensive-rats
#4
María Elvira Brocca, Luciana Pietranera, Maria Meyer, Analia Lima, Paulina Roig, E Ronald de Kloet, Alejandro F De Nicola
Damage observed in the hippocampus of the adult spontaneously hypertensive rat (SHR) resembles the neuropathology of mineralocorticoid-induced hypertension, supporting a similar endocrine dysfunction in both entities. In this study we have tested the hypothesis that increased expression of the hippocampal mineralocorticoid receptor (MR) in SHR animals is associated with a prevalent expression of pro-inflammatory over anti-inflammatory factors. For this purpose we measured in hippocampus mRNA expression and immunoreactivity of the MR and the glucocorticoid receptor (GR) using qPCR and histochemistry...
May 18, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28515448/involvement-of-vascular-aldosterone-synthase-in-phosphate-induced-osteogenic-transformation-of-vascular-smooth-muscle-cells
#5
Ioana Alesutan, Jakob Voelkl, Martina Feger, Denise V Kratschmar, Tatsiana Castor, Sobuj Mia, Michael Sacherer, Robert Viereck, Oliver Borst, Christina Leibrock, Meinrad Gawaz, Makoto Kuro-O, Stefan Pilz, Andreas Tomaschitz, Alex Odermatt, Burkert Pieske, Carsten A Wagner, Florian Lang
Vascular calcification resulting from hyperphosphatemia is a major determinant of mortality in chronic kidney disease (CKD). Vascular calcification is driven by aldosterone-sensitive osteogenic transformation of vascular smooth muscle cells (VSMCs). We show that even in absence of exogenous aldosterone, silencing and pharmacological inhibition (spironolactone, eplerenone) of the mineralocorticoid receptor (MR) ameliorated phosphate-induced osteo-/chondrogenic transformation of primary human aortic smooth muscle cells (HAoSMCs)...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28513758/-new-drugs-for-small-animals-in-2016
#6
Ilka Ute Emmerich
In 2016, two active pharmaceutical ingredients were released on the German market for small animals: the mineralocorticoid Desoxycorticosterone (Zycortal(®)) and Sarolaner (Simparica(®)), an ectoparasiticide of the isoxazoline group. One substance has been authorized for an additional species; Fluralaner (Bravecto(®)), also an ectoparasiticide of the isoxazoline group, is now authorized for use in cats. Additionally, one veterinary drug with a new combination of active ingredients, one active substance in mono-preparation and two veterinary drugs with a new pharmaceutical form have been launched on the market for small animals...
May 17, 2017: Tierärztliche Praxis. Ausgabe K, Kleintiere/Heimtiere
https://www.readbyqxmd.com/read/28511711/sglt2-inhibitors-a-novel-choice-for-the-combination-therapy-in-diabetic-kidney-disease
#7
REVIEW
Honghong Zou, Baoqin Zhou, Gaosi Xu
Diabetic kidney disease (DKD) is the most common cause of end stage renal disease. The comprehensive management of DKD depends on combined target-therapies for hyperglycemia, hypertension, albuminuria, and hyperlipaemia, etc. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, the most recently developed oral hypoglycemic agents acted on renal proximal tubules, suppress glucose reabsorption and increase urinary glucose excretion. Besides improvements in glycemic control, they presented excellent performances in direct renoprotective effects and the cardiovascular (CV) safety by decreasing albuminuria and the independent CV risk factors such as body weight and blood pressure, etc...
May 16, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28508605/disorders-of-adrenal-steroidogenesis-impact-on-gonadal-function-and-sex-development
#8
Christiaan F Mooij, Antonius E van Herwaarden, Hedi L Claahsen-van der Grinten
A defect in adrenal steroidogenesis may cause a disorder of sex development (DSD). Importantly, DSD of adrenal origin is not restricted to a genital phenotype but is in most cases accompanied by mild to severe impairment in glucocorticoid and/or mineralocorticoid synthesis. If a patient is suspected of DSD of adrenal origin evaluation of glucocorticoid and mineralocorticoid metabolism is therefore essential to provide adequate medical care in the case of a severe and potentially life-threatening insufficiency...
December 2016: Pediatric Endocrinology Reviews: PER
https://www.readbyqxmd.com/read/28495982/a-new-role-of-mister-mr-t-in-hypertension-mineralocorticoid-receptor-immune-system-and-hypertension
#9
EDITORIAL
Natalia R Barbaro, Annet Kirabo, David G Harrison
No abstract text is available yet for this article.
May 12, 2017: Circulation Research
https://www.readbyqxmd.com/read/28493961/aldosterone-signaling-regulates-the-over-expression-of-claudin-4-and-8-at-the-distal-nephron-from-type-1-diabetic-rats
#10
Eduardo Molina-Jijón, Rafael Rodríguez-Muñoz, Ricardo González-Ramírez, Carmen Namorado-Tónix, José Pedraza-Chaverri, Jose L Reyes
Hyperglycemia in diabetes alters tight junction (TJ) proteins in the kidney. We evaluated the participation of aldosterone (ALD), and the effect of spironolactone (SPL), a mineralocorticoid receptor antagonist, on the expressions of claudin-2, -4, -5 and -8, and occludin in glomeruli, proximal and distal tubules isolated from diabetic rats. Type 1 diabetes was induced in female Wistar rats by a single tail vein injection of streptozotocin (STZ), and SPL was administrated daily by gavage, from days 3-21. Twenty-one days after STZ injection the rats were sacrificed...
2017: PloS One
https://www.readbyqxmd.com/read/28493291/prevalence-of-primary-aldosteronism-among-patients-with-type-2-diabetes
#11
M Tancredi, G Johansson, B Eliasson, R Eggertsen, U Lindblad, S Dahlqvist, H Imberg, M Lind
CONTEXT: Diabetes and hypertension coexist in 40-60% of individuals with type 2 diabetes. The coexistence of this two conditions is associated with increased risk of retinopathy, nephropathy and cardiovascular disease. OBJECTIVE: To investigate the prevalence of primary aldosteronism (PA) in a general cohort of persons with type 2 diabetes. DESIGN: Cross-sectional study involving 6 diabetes outpatient clinics in Sweden. PATIENTS: Were enrolled individuals with type 2 diabetes between February 2008 and December 2013...
May 10, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28492512/aldosterone-and-mineralocorticoid-receptors-physiology-and-pathophysiology
#12
John W Funder
Aldosterone is a uniquely terrestrial hormone, first appearing in lungfish, which have both gills and lungs. Mineralocorticoid receptors (MRs), on the other hand, evolved much earlier, and are found in cartilaginous and bony fish, presumptive ligand cortisol. MRs have equivalent high affinity for aldosterone, progesterone, and cortisol; in epithelia, despite much higher cortisol circulating levels, aldosterone selectively activates MRs by co-expression of the enzyme 11β-hydroxysteroid dehydrogenase, Type 11...
May 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28490690/a-decline-in-female-baboon-hypothalamo-pituitary-adrenal-axis-activity-anticipates-aging
#13
Shanshan Yang, Kenneth G Gerow, Hillary F Huber, McKenna M Considine, Cun Li, Vicki Mattern, Anthony G Comuzzie, Stephen P Ford, Peter W Nathanielsz
Stressors that disrupt homeostasis advance aging. Glucocorticoids regulate multiple processes that determine the aging trajectory. Debate exists regarding life-course circulating glucocorticoid concentrations. Rodent and nonhuman primate studies indicate circulating glucocorticoids fall from early life. We measured fasting morning cortisol in 24 female baboons (6-21 years, human equivalent ~18-70). We also quantified hypothalamic paraventricular nuclear (PVN) arginine vasopressin (AVP), corticotropin-releasing hormone, steroid receptors, and pituitary proopiomelanocortin immunohistochemically in 14 of these females at 6-13 years...
May 9, 2017: Aging
https://www.readbyqxmd.com/read/28476146/heart-failure-in-patients-with-coronary-heart-disease-prevalence-characteristics-and-guideline-implementation-results-from-the-german-euroaspire-iv-cohort
#14
Caroline Morbach, Martin Wagner, Stefan Güntner, Carolin Malsch, Mehmet Oezkur, David Wood, Kornelia Kotseva, Rainer Leyh, Georg Ertl, Wolfgang Karmann, Peter U Heuschmann, Stefan Störk
BACKGROUND: Adherence to pharmacotherapeutic treatment guidelines in patients with heart failure (HF) is of major prognostic importance, but thorough implementation of guidelines in routine care remains insufficient. Our aim was to investigate prevalence and characteristics of HF in patients with coronary heart disease (CHD), and to assess the adherence to current HF guidelines in patients with HF stage C, thus identifying potential targets for the optimization of guideline implementation...
May 5, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28476142/dipeptidyl-peptidase-4-dpp-4-inhibition-with-linagliptin-reduces-western-diet-induced-myocardial-traf3ip2-expression-inflammation-and-fibrosis-in-female-mice
#15
Annayya R Aroor, Javad Habibi, Hemanth Kumar Kandikattu, Mona Garro-Kacher, Brady Barron, Dongqing Chen, Melvin R Hayden, Adam Whaley-Connell, Shawn B Bender, Thomas Klein, Jaume Padilla, James R Sowers, Bysani Chandrasekar, Vincent G DeMarco
BACKGROUND: Diastolic dysfunction (DD), a hallmark of obesity and primary defect in heart failure with preserved ejection fraction, is a predictor of future cardiovascular events. We previously reported that linagliptin, a dipeptidyl peptidase-4 inhibitor, improved DD in Zucker Obese rats, a genetic model of obesity and hypertension. Here we investigated the cardioprotective effects of linagliptin on development of DD in western diet (WD)-fed mice, a clinically relevant model of overnutrition and activation of the renin-angiotensin-aldosterone system...
May 5, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28472300/interaction-of-the-mineralocorticoid-receptor-with-rack1-and-its-role-in-aldosterone-signaling
#16
Maniselvan Kuppusamy, Elise P Gomez-Sanchez, Lauren N Beloate, Maria Plonczynski, Aniko Naray-Fejes-Toth, Geza Fejes-Toth, Celso E Gomez-Sanchez
The mineralocorticoid receptor (MR) is a member of the steroid-thyroid hormone receptor superfamily of ligand-dependent transcription factors with diverse functions including the biological actions of aldosterone. Identification of the various transcriptional co-regulators of MR is essential for understanding the complexity of MR signaling pathways under physiological and pathological conditions. We used a yeast two-hybrid system to find proteins that interact with a full-length MR and found, among other proteins, that MR interacted specifically with Receptor for Activated C Kinase 1 (RACK1), a scaffolding protein...
May 2, 2017: Endocrinology
https://www.readbyqxmd.com/read/28468932/evolution-of-the-mineralocorticoid-receptor-sequence-structure-and-function
#17
Michael E Baker, Yoshinao Katsu
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 chimaeras. 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...
May 3, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28465238/repetitive-stress-leads-to-impaired-cognitive-function-that-is-associated-with-dna-hypomethylation-reduced-bdnf-and-a-dysregulated-hpa-axis
#18
Khayelihle B Makhathini, Oualid Abboussi, Dan J Stein, Musa V Mabandla, William M U Daniels
Exposure to repetitive stress has a negative influence on cognitive-affective functioning, with growing evidence that these effects may be mediated by a dysregulated hypothalamic-pituitary-adrenal (HPA) axis, abnormal neurotrophic factor levels and its subsequent impact on hippocampal function. However, there are few data about the effect of repetitive stressors on epigenetic changes in the hippocampus. In the present study, we examine how repetitive restrain stress (RRS) affects cognitive-affective functioning, HPA axis regulation, brain-derived neurotrophic factor (BDNF) levels, and global hippocampal DNA methylation...
April 29, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28463464/physicians-guideline-adherence-is-associated-with-better-prognosis-in-outpatients-with-heart-failure-with-reduced-ejection-fraction-the-qualify-international-registry
#19
Michel Komajda, Martin R Cowie, Luigi Tavazzi, Piotr Ponikowski, Stefan D Anker, Gerasimos S Filippatos
AIMS: To evaluate the impact of physicians' adherence to guideline-recommended medications for heart failure with reduced ejection fraction (HFrEF), including ≥50% prescription of recommended doses, on clinical outcomes at 6-month follow-up. METHODS AND RESULTS: In QUALIFY, an international, prospective, observational, longitudinal survey, 6669 outpatients with HFrEF were recruited 1-15 months after heart failure (HF) hospitalization from September 2013 to December 2014 in 36 countries and followed up at 6 months...
April 30, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28461696/a-relationship-between-the-aldosterone-mineralocorticoid-receptor-pathway-and-alcohol-drinking-preliminary-translational-findings-across-rats-monkeys-and-humans
#20
E G Aoun, V A Jimenez, L F Vendruscolo, N A R Walter, E Barbier, A Ferrulli, C L Haass-Koffler, P Darakjian, M R Lee, G Addolorato, M Heilig, R Hitzemann, G F Koob, K A Grant, L Leggio
Aldosterone regulates electrolyte and fluid homeostasis through binding to the mineralocorticoid receptors (MRs). Previous work provides evidence for a role of aldosterone in alcohol use disorders (AUDs). We tested the hypothesis that high functional activity of the mineralocorticoid endocrine pathway contributes to vulnerability for AUDs. In Study 1, we investigated the relationship between plasma aldosterone levels, ethanol self-administration and the expression of CYP11B2 and MR (NR3C2) genes in the prefrontal cortex area (PFC) and central nucleus of the amygdala (CeA) in monkeys...
May 2, 2017: Molecular Psychiatry
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