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.
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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 |
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