Activation of a Membrane-associated Androgen Receptor Promotes Cell Death in Primary Cortical Astrocytes.
From: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, Texas 76107-2699, USA.
Endocrinology
- Publish Date: May 2007
- ISSN: 0013-7227
- Volume: 148
- Issue: 5
- Pages: 2458-64
- Medium: Print
- Language: English
- Citation (JAMA): Gatson Joshua W, Singh Meharvan, et al. Activation of a Membrane-associated Androgen Receptor Promotes Cell Death in Primary Cortical Astrocytes.. Endocrinology May 2007;148:2458-64
Abstract
In the central nervous system, androgens can exert either protective or damage-promoting effects. For example, testosterone protects neurons against beta-amyloid toxicity, whereas in other studies, testosterone exacerbated stroke-induced lesion size. The mechanism underlying this duality of androgens is still unclear. Recently, our laboratory reported that androgens elicit opposite effects on the ERK/MAPK and Akt signaling pathways, depending on whether a membrane androgen receptor (AR) or intracellular AR was activated. By extension, we hypothesized that androgens may affect cell viability differently depending on which receptor is activated. Here, we found that dihydrotestosterone (DHT) protected primary cortical astrocytes from the metabolic and oxidative insult associated with iodoacetic acid-induced toxicity, whereas DHT-BSA, a cell impermeable analog of DHT that preferentially targets the membrane AR, suppressed Akt signaling, increased caspase 3/7 activity, and enhanced iodoacetic acid-induced cell death. Interestingly, DHT-BSA also blocked the protective effects of DHT and estradiol. Collectively, these data support the existence of two, potentially competing, pathways for androgens in a given cell or tissue that may provide insight into the controversy of whether androgen therapy is beneficial or detrimental.
Mesh Headings (Keywords): Androgens, Animals, Apoptosis, Astrocytes, Caspase 3, Caspase 7, Cell Survival, Cells, Cultured, Cerebral Cortex, Dihydrotestosterone, Enzyme Inhibitors, Estradiol, Iodoacetic Acid, Membrane Proteins, Mice, Mice, Inbred C57BL, Proto-Oncogene Proteins c-akt, Receptors, Androgen, Signal Transduction
Check for Full Text / PubMed Unique Identifier (PMID): 17303658
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.