Cited by 269Estrogen and related hormone effectsHormonal and reproductive studiesIon channel regulation and function

Testosterone stimulates intracellular calcium release and mitogen-activated protein kinases via a G protein-coupled receptor in skeletal muscle cells

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Estrada, Manuel, Espinosa, Alejandra, Müller, Marioly, Jaimovich, Enrique·2003·Endocrinology

Abstract

Involvement of intracellular Ca(2+) and ERK1/2 phosphorylation in the fast nongenomic effects of androgens in myotubes was investigated. Testosterone or nandrolone produced fast (<1 min) and transient increases in intracellular Ca(2+) with an oscillatory pattern. Calcium signals were slightly reduced in Ca(2+)-free medium, but lack of oscillations was evident. Signals were blocked by U-73122 and xestospongin B, inhibitors of inositol 1,4,5-trisphosphate (IP(3)) pathway. Furthermore, IP(3) increased transiently 2- to 3-fold 45 sec after hormone addition. Cyproterone neither affected the fast Ca(2+) signal nor the increase in IP(3). Calcium increases could also be induced by the impermeant testosterone conjugated to BSA, and the effect of testosterone was abolished in cells incubated with guanosine 5'-O-(2-thiodiphosphate) or pertussis toxin. Stimulation of myotubes with testosterone, nandrolone, or testosterone conjugated to BSA increased immunodetectable phosphorylation of ERK1/2 within 5 min, and this effect was not inhibited by cyproterone. Phosphorylation was blocked by the use of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethylester, U-73122, and xestospongin B as well as by dominant negative Ras, MAPK kinase (MEK), or the MEK inhibitor PD-98059. In addition, guanosine 5'-O-(2-thiodiphosphate) or pertussis toxin blocked ERK1/2 phosphorylation. These results are consistent with a fast effect of testosterone, involving a G protein-linked receptor at the plasma membrane, IP(3)-mediated Ca(2+) signal, and the Ras/MEK/ERK pathway in muscle cells.

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Crossref · 10.1210/en.2002-0164

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Authors
Estrada, M., Espinosa, A., Müller, M., & Jaimovich, E.
Affiliations
University of Chile (CL)
Corresponding author
Jaimovich, Enrique
Venue
Endocrinology
Published
2003-08
Volume
144
Issue
8
Pages
3586-3597
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
OpenAlex
W2134223482
Cited by
264
References
46
Citations by year
2026: 6 · 2025: 8 · 2024: 17 · 2023: 14 · 2022: 8 · 2021: 11 · 2020: 13 · 2019: 9 · 2018: 8 · 2017: 8 · 2016: 14 · 2015: 13 · 2014: 8 · 2013: 13 · 2012: 9
FWCI
5.16
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Americanae (AECID Library) (submittedVersion, other-oa)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
Funders
Olympus
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
testosterone, nandrolone, intracellular calcium release, calcium oscillations, inositol 1,4,5-trisphosphate, IP3 receptor, ERK1/2 phosphorylation, Ras/MEK/ERK signaling, G protein-coupled receptors, skeletal muscle myotubes, cyproterone, pertussis toxin, MEK inhibitors
MeSH terms
Androgens, Animals, Animals, Newborn, Calcium, Chelating Agents, Nandrolone, Phosphorylation, Testosterone, Transfection, Calcium Channels, Inositol 1,4,5-Trisphosphate, Gene Expression, Protein Serine-Threonine Kinases, Cyclic AMP Response Element-Binding Protein, Cyproterone Acetate, Receptors, Cytoplasmic and Nuclear, Muscle, Skeletal, Muscle Fibers, Skeletal, ras Proteins, GTP-Binding Proteins, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3, Rats, Inositol 1,4,5-Trisphosphate Receptors, Androgen Receptor Antagonists

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