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Testosterone Induces an Intracellular Calcium Increase by a Nongenomic Mechanism in Cultured Rat Cardiac Myocytes
Abstract
Androgens are associated with important effects on the heart, such as hypertrophy or apoptosis. These responses involve the intracellular androgen receptor. However, the mechanisms of how androgens activate several membrane signaling pathways are not fully elucidated. We have investigated the effect of testosterone on intracellular calcium in cultured rat cardiac myocytes. Using fluo3-AM and epifluorescence microscopy, we found that exposure to testosterone rapidly (1-7 min) led to an increase of intracellular Ca2+, an effect that persisted in the absence of external Ca2+. Immunocytochemical analysis showed that these effects occurred before translocation of the intracellular androgen receptor to the perinuclear zone. Pretreatment of the cells with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethylester and thapsigargin blocked this response, suggesting the involvement of internal Ca2+ stores. U-73122, an inhibitor of phospholipase C, and xestospongin C, an inhibitor of inositol 1,4,5-trisphosphate receptor, abolished the Ca2+ signal. The rise in intracellular Ca2+ was not inhibited by cyproterone, an antagonist of intracellular androgen receptor. Moreover, the cell impermeant testosterone-BSA complex also produced the Ca2+ signal, indicating its origin in the plasma membrane. This effect was observed in cultured neonatal and adult rat cardiac myocytes. Pertussis toxin and the adenoviral transduction of beta- adrenergic receptor kinase carboxy terminal peptide, a peptide inhibitor of betagamma-subunits of G protein, abolished the testosterone-induced Ca2+ release. In summary, this is the first study of rapid, nongenomic intracellular Ca2+ signaling of testosterone in cardiac myocytes. Using various inhibitors and testosterone-BSA complex, the mechanism for the rapid, testosterone-induced increase in intracellular Ca2+ is through activation of a plasma membrane receptor associated with a Pertussis toxin-sensitive G protein-phospholipase C/inositol 1,4,5-trisphosphate signaling pathway.
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“Mammalian steroid hormones increase Ca2+ influx in a variety of cell types, including cardiac myocytes and skeletal muscle182,183.”
From The Phytochemical, Biological, and Medicinal Attributes of Phytoecdysteroids: An Updated Review (2021) · cites this paper as [183]
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Metadata
- Authors
- Vicencio, J. M., Ibarra, C., Estrada, M., Chiong, M., Soto, D., Parra, V., Diaz-Araya, G., Jaimovich, E., & Lavandero, S.
- Affiliations
- University of Chile (CL)
- Corresponding author
- Jaimovich, Enrique
- Lavandero, Sergio
- ORCID
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2006-03-01
- Volume
- 147
- Issue
- 3
- Pages
- 1386-1395
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2026135073
- Cited by
- 149
- References
- 60
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 6 · 2023: 3 · 2022: 5 · 2021: 7 · 2020: 7 · 2019: 9 · 2018: 7 · 2017: 6 · 2016: 8 · 2015: 6 · 2014: 4 · 2013: 13 · 2012: 9
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Universidad de Chile (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- testosterone, intracellular calcium, cardiomyocytes, plasma membrane receptors, G protein beta gamma subunits, phospholipase C, IP3 receptor, intracellular calcium stores, androgen receptor, beta-adrenergic receptor kinase, pertussis toxin
- MeSH terms
- Adenoviridae, Albumins, Aniline Compounds, Animals, Animals, Newborn, Calcium, Cells, Cultured, Estrenes, Fluorescent Dyes, Genetic Vectors, Image Processing, Computer-Assisted, Immunohistochemistry, Microscopy, Fluorescence, Peptides, Type C Phospholipases, Pyrrolidinones, Testosterone, Xanthenes, Models, Statistical, Signal Transduction, Inositol 1,4,5-Trisphosphate, Apoptosis, Thapsigargin, Myocytes, Cardiac, Pertussis Toxin, Rats
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