Abstract
Increasing evidence suggests that nongenomic effects of testosterone and anabolic androgenic steroids (AAS) operate concertedly with genomic effects. Classically, these responses have been viewed as separate and independent processes, primarily because nongenomic responses are faster and appear to be mediated by membrane androgen receptors, whereas long-term genomic effects are mediated through cytosolic androgen receptors regulating transcriptional activity. Numerous studies have demonstrated increases in intracellular Ca2+ in response to AAS. These Ca2+ mediated responses have been seen in a diversity of cell types, including osteoblasts, platelets, skeletal muscle cells, cardiac myocytes and neurons. The versatility of Ca2+ as a second messenger provides these responses with a vast number of pathophysiological implications. In cardiac cells, testosterone elicits voltage-dependent Ca2+ oscillations and IP3Rmediated Ca2+ release from internal stores, leading to activation of MAPK and mTOR signaling that promotes cardiac hypertrophy. In neurons, depending upon concentration, testosterone can provoke either physiological Ca2+ oscillations, essential for synaptic plasticity, or sustained, pathological Ca2+ transients that lead to neuronal apoptosis. We propose therefore, that Ca2+ acts as an important point of crosstalk between nongenomic and genomic AAS signaling, representing a central regulator that bridges these previously thought to be divergent responses.
Keywords: Androgens, Ca2+, cardiac myocytes, heart, genomic, neurons, nongenomic, skeletal muscle cells, testosterone, Anabolic Androgenic Steroids, Intracellular Calcium Signaling, Physiological Implications
Mini-Reviews in Medicinal Chemistry
Title: Anabolic Androgenic Steroids and Intracellular Calcium Signaling: A Mini Review on Mechanisms and Physiological Implications
Volume: 11 Issue: 5
Author(s): J. M. Vicencio, M. Estrada, D. Galvis, R. Bravo, A. E. Contreras, D. Rotter, G. Szabadkai, J. A. Hill, B. A. Rothermel, E. Jaimovich and S. Lavandero
Affiliation:
Keywords: Androgens, Ca2+, cardiac myocytes, heart, genomic, neurons, nongenomic, skeletal muscle cells, testosterone, Anabolic Androgenic Steroids, Intracellular Calcium Signaling, Physiological Implications
Abstract: Increasing evidence suggests that nongenomic effects of testosterone and anabolic androgenic steroids (AAS) operate concertedly with genomic effects. Classically, these responses have been viewed as separate and independent processes, primarily because nongenomic responses are faster and appear to be mediated by membrane androgen receptors, whereas long-term genomic effects are mediated through cytosolic androgen receptors regulating transcriptional activity. Numerous studies have demonstrated increases in intracellular Ca2+ in response to AAS. These Ca2+ mediated responses have been seen in a diversity of cell types, including osteoblasts, platelets, skeletal muscle cells, cardiac myocytes and neurons. The versatility of Ca2+ as a second messenger provides these responses with a vast number of pathophysiological implications. In cardiac cells, testosterone elicits voltage-dependent Ca2+ oscillations and IP3Rmediated Ca2+ release from internal stores, leading to activation of MAPK and mTOR signaling that promotes cardiac hypertrophy. In neurons, depending upon concentration, testosterone can provoke either physiological Ca2+ oscillations, essential for synaptic plasticity, or sustained, pathological Ca2+ transients that lead to neuronal apoptosis. We propose therefore, that Ca2+ acts as an important point of crosstalk between nongenomic and genomic AAS signaling, representing a central regulator that bridges these previously thought to be divergent responses.
Export Options
About this article
Cite this article as:
M. Vicencio J., Estrada M., Galvis D., Bravo R., E. Contreras A., Rotter D., Szabadkai G., A. Hill J., A. Rothermel B., Jaimovich E. and Lavandero S., Anabolic Androgenic Steroids and Intracellular Calcium Signaling: A Mini Review on Mechanisms and Physiological Implications, Mini-Reviews in Medicinal Chemistry 2011; 11 (5) . https://dx.doi.org/10.2174/138955711795445880
DOI https://dx.doi.org/10.2174/138955711795445880 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Resveratrol and Clinical Trials: The Crossroad from In Vitro Studies to Human Evidence
Current Pharmaceutical Design Primary Hyperaldosteronism in the Hypertensive Disease
Current Hypertension Reviews Attention Deficit Hyperactive Disorder and Occurrence of Tic Disorders in Children and Adolescents—What is the Verdict
Current Pediatric Reviews Human Heart Failure: A Proteomics Perspective
Current Proteomics Hypotensive Peptides from Snake Venoms: Structure, Function and Mechanism
Current Topics in Medicinal Chemistry Acute Coronary Syndromes in Patients with Atrial Fibrillation and Heart Failure. Could Novel Oral Anticoagulants be the Solution of the Optimal Antithrombotic Therapy Puzzle?
Cardiovascular & Hematological Agents in Medicinal Chemistry “Endothelial Progenitor Cells” as a Therapeutic Strategy in Cardiovascular Disease
Current Vascular Pharmacology The Entirely Subcutaneous Defibrillator (S-Icd): State of the Art and Selection of the Ideal Candidate
Current Cardiology Reviews Patent Selections :
Recent Patents on Cardiovascular Drug Discovery Cardiovascular Magnetic Resonance Imaging: State of the Art
Current Cardiology Reviews Does Caffeine Affect Cardiovascular Responses?
Vascular Disease Prevention (Discontinued) Psoriasis and Vascular Risk : An Update
Current Pharmaceutical Design Vasopressin and Oxytocin in Control of the Cardiovascular System
Current Neuropharmacology Steroidal Cardiac Na<sup>+</sup>/K<sup>+</sup> ATPase Inhibitors Exhibit Strong Anti-Cancer Potential <i>in vitro</i> and in Prostate and Lung Cancer Xenografts <i>in vivo</i>
Anti-Cancer Agents in Medicinal Chemistry Homocysteine and Heart Failure: An Overview
Recent Patents on Cardiovascular Drug Discovery Impact of Ultrasound Contrast Agents in Echocardiographic Assessment of Ischemic Heart Disease
Recent Patents on Cardiovascular Drug Discovery Dysregulation of Acetylation Enzymes Inanimal Models of Psychostimulant use Disorders: Evolving Stories
Current Neuropharmacology Subject Index To Volume 12
Current Pharmaceutical Design The Role of Brain Gaseous Transmitters in the Regulation of the Circulatory System
Current Pharmaceutical Biotechnology Amiodarone Hepatotoxicity
Current Vascular Pharmacology