Transcriptional activation of elephant shark mineralocorticoid receptor by corticosteroids, progesterone, and spironolactone

The mineralocorticoid receptor (MR) is a nuclear receptor and part of a large and diverse family of transcription factors that also includes receptors for glucocorticoids, progesterone, androgens, and estrogens. The corticosteroid aldosterone is the physiological activator of the MR in humans and other terrestrial vertebrates; however, its activator is not known in cartilaginous fish, the oldest group of extant jawed vertebrates. Here, we analyzed the ability of corticosteroids and progesterone to activate the full-length MR from the elephant shark (Callorhinchus milii). On the basis of their measured activities, aldosterone, cortisol, 11-deoxycorticosterone, corticosterone, 11-deoxcortisol, progesterone, and 19-norprogesterone are potential physiological mineralocorticoids. However, aldosterone, the physiological mineralocorticoid in humans and other terrestrial vertebrates, is not found in cartilaginous or ray-finned fish. Although progesterone activates MRs in ray-finned fish, progesterone does not activate MRs in humans, amphibians, or alligator, suggesting that during the transition to terrestrial vertebrates, progesterone lost the ability to activate the MR. Both elephant shark MR and human MR are expressed in the brain, heart, ovary, testis, and other nonepithelial tissues, suggesting that MR expression in diverse tissues evolved in the common ancestor of jawed vertebrates. Our data suggest that 19-norprogesterone– and progesterone-activated MR may have unappreci...
Source: Signal Transduction Knowledge Environment - Category: Science Authors: Tags: STKE Research Articles Source Type: news

Related Links:

ConclusionsThe results of this meta-analysis show that LABA/LAMA combinations are consistently more effective than ICS/LABA FDCs for most of the evaluated outcomes. However, differences have also been observed between FDCs belonging to the same class. Across the investigated LABA/LAMA FDCs, glycopyrronium/indacaterol revealed a consistent and robust efficacy profile.
Source: Pulmonary Pharmacology and Therapeutics - Category: Respiratory Medicine Source Type: research
Publication date: Available online 19 October 2019Source: Autoimmunity ReviewsAuthor(s): Jelena Blagojevic, Paul Legendre, Marco Matucci-Cerinic, Luc MouthonAbstractIn systemic sclerosis (SSc), the use of corticosteroids (CS) is controversial due to their association with scleroderma renal crisis (SRC). However, patients with very early and early disease, characterised by main inflammatory component, may benefit from CS therapy.The aim of this review is to discuss pros and cons of CS treatment in SSc, providing current evidence about the use of CS in SSc. Moreover, we discuss also the underlying pathogenetic mechanisms tha...
Source: Autoimmunity Reviews - Category: Allergy & Immunology Source Type: research
Authors: Macomb CV, Evans MO, Dockstater JE, Montgomery JR, Beakes DE Abstract Shoulder injury related to vaccine administration (SIRVA) is defined as "shoulder pain with limited range of motion within 48 hours after vaccine receipt in individuals with no prior history of pain, inflammation, or dysfunction of the affected shoulder before vaccine administration." Corticosteroid injections (CSIs) have been proposed as a reasonable treatment modality for SIRVA, although evidence regarding efficacy is scanty. In this case series, we present two patients diagnosed with SIRVA who received CSI within 5 days of s...
Source: Military Medicine - Category: International Medicine & Public Health Tags: Mil Med Source Type: research
Conclusions: It was estimated that the economic impact of a severe exacerbation in Spanish patients with severe asthma was €758.7/exacerbation. PMID: 31621441 [PubMed - as supplied by publisher]
Source: Journal of Asthma - Category: Respiratory Medicine Tags: J Asthma Source Type: research
Publication date: Available online 18 October 2019Source: Physiology &BehaviorAuthor(s): Dennis F. Lovelock, Terrence DeakAbstractAdolescence is a developmental epoch marked by maturation of stress-responsive systems including the Hypothalamic-Pituitary-Adrenal (HPA) axis. Emerging evidence has found sex-specificity in the long term behavioral and neural effects of stressors experienced during this sensitive period, though most studies have utilized chronic stress exposures that span much of the adolescent period. Using Sprague-Dawley rats, we examined how a single exposure to inescapable footshock (80 shocks, 5s, 1.0 ...
Source: Physiology and Behavior - Category: Physiology Source Type: research
Introduction Ozone has been recently used as a safe alternative treatment in musculoskeletal disorders with fewer adverse effects than corticosteroids. The aim of this study was to compare the efficacy of a single injection of ozone with that of a corticosteroid in the treatment of shoulder impingement. Design Thirty patients with shoulder pain and clinical signs and symptoms of impingement were randomly assigned into two groups: ultrasound-guided injection with ozone or corticosteroid. Patients’ symptoms were evaluated by visual analog scale, constant score, shoulder pain and disability scale, shoulder range of...
Source: American Journal of Physical Medicine and Rehabilitation - Category: Rehabilitation Tags: Original Research Articles Source Type: research
Authors: Zhang W Abstract Osteoarthritis (OA) is the most common form of arthritis. Pain and its related function and stiffness are currently the major symptoms and primary outcomes for treatment. However, the treatment in the past has been primarily targeting on the peripheral changes in the joint that has led to suboptimal outcomes. Recently, we find that people with OA respond better to treatment which targets on both peripheral and central pain abnormalities. We also find that placebo per se is very effective for OA. On average 75% pain reduction, 71% functional improvement and 83% stiffness improvement in the ...
Source: Clinical and Experimental Rheumatology - Category: Rheumatology Tags: Clin Exp Rheumatol Source Type: research
ConclusionsThe macrolide antibiotics treatment has beneficial effects on lung function in non-asthmatic chronic cough patients with normal chest X-ray findings. The improvement of chronic rhinosinusitis may have some role in the lung condition. Upper respiratory tract examination and treatment may be useful for the management of chronic cough.
Source: American Journal of Otolaryngology - Category: Endocrinology Source Type: research
We report post hoc analyses of pooled data from duplicate, placebo-controlled Phase 3 trials. Patients aged 12–75 with inadequately controlled, moderate-to-severe asthma were randomized 1:1 to receive intravenous reslizumab 3.0 mg/kg or placebo every 4 weeks for 52 weeks, stratified by oral corticosteroid use at enrollment and by region. Assessments included efficacy and predictors of clinical asthma exacerbation response in oral corticosteroid-dependent patients, and systemic corticosteroids burden in the overall population.RESULTSPatients were randomized to reslizumab (n = 477) or placebo (n = 476); 73 (15%) patien...
Source: The Journal of Allergy and Clinical Immunology: In Practice - Category: Allergy & Immunology Source Type: research
Conclusions: Drug-resistant CMVR is a complex clinical challenge. Multiple systemic and local treatment strategies may be necessary but toxicity, resistance, and co-morbidities may severely restrict available options. PMID: 31621449 [PubMed - as supplied by publisher]
Source: Ocular Immunology and Inflammation - Category: Allergy & Immunology Tags: Ocul Immunol Inflamm Source Type: research
More News: Brain | Cardiology | Corticosteroid Therapy | Environmental Health | Fish | Heart | Neurology | Ovaries | Physiology | Science | Spironolactone