Anabolic Androgenic Steroids and Intracellular Calcium Signaling: A Mini Review on Mechanisms and Physiological Implications
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: FONDAP Center for Molecular Studies of the Cell, Faculty of Chemical and Pharmaceutical Sciences/Faculty of Medicine, University of Chile, Olivos 1007, Santiago 8380492, Chile.
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
Rights & PermissionsPrintExport