The Role of a Membrane Androgen Receptron in the Brain
type: CreativeWork
description: Gatson, Joshua Wayne, The Role of a Membrane Androgen Receptor in the Brain. Doctor of Philosophy (Biomedical Sciences), February 2007, pp187, 34 illustrations. In the brain, depending on the insult type, androgens have been shown to protect from or exacerbate the levels of cell death. This discrepancy is partly due to the array of receptors that androgens may activate during injury. For example, activation of intracellular androgen receptors (AR) leads to the activation of pro-survival pathways and protects from various toxins such beta-amyloid. In contrast, previous studies have demonstrated that testosterone causes an increase in lesion size following stroke. The damaging effects of androgens in the brain may be mediated by a membrane-associated AR (mAR), since activation of mAR in peripheral tissue results in a decrease in cell growth and an increase in apoptotic cell death during serum deprivation. Here, I hypothesize that activation of a mAR in cortical astrocytes, suppresses the ERK and Akt signaling pathways and increases cell death in the presence of a metabolic and oxidative stressor. In this study, we found that glia express both isoforms of the AR (AR-B and AR-A) and that dihydrotestosterone (DHT) elicits ERK and Akt phosphorylation in rat glioma (C6) cells. The effect of DHT on the activation of these signaling pathways is AR dependent, since flutamide blocked this effect. In contrast to the intracellular receptor, we concluded that DHT-BSA (membrane impermeant form of DHT) binds to DHT displaceable sites on the plasma membrane. Also, treatment with DHT-BSA in the C6 cells resulted in a significant decrease in phosphor-ERK and Akt levels, suggesting the existence of two different pathways through which DHT can influence the activity of these signaling pathways. With respect to cell survival, the C6 cells and primary cortical astrocytes were treated with the metabolic and oxidative insult, iodoacetic acid (IAA), in the presence or absence of DHT, DHT-BSA…
abstract: Gatson, Joshua Wayne, The Role of a Membrane Androgen Receptor in the Brain. Doctor of Philosophy (Biomedical Sciences), February 2007, pp187, 34 illustrations. In the brain, depending on the insult type, androgens have been shown to protect from or exacerbate the levels of cell death. This discrepancy is partly due to the array of receptors that androgens may activate during injury. For example, activation of intracellular androgen receptors (AR) leads to the activation of pro-survival pathways and protects from various toxins such beta-amyloid. In contrast, previous studies have demonstrated that testosterone causes an increase in lesion size following stroke. The damaging effects of androgens in the brain may be mediated by a membrane-associated AR (mAR), since activation of mAR in peripheral tissue results in a decrease in cell growth and an increase in apoptotic cell death during serum deprivation. Here, I hypothesize that activation of a mAR in cortical astrocytes, suppresses the ERK and Akt signaling pathways and increases cell death in the presence of a metabolic and oxidative stressor. In this study, we found that glia express both isoforms of the AR (AR-B and AR-A) and that dihydrotestosterone (DHT) elicits ERK and Akt phosphorylation in rat glioma (C6) cells. The effect of DHT on the activation of these signaling pathways is AR dependent, since flutamide blocked this effect. In contrast to the intracellular receptor, we concluded that DHT-BSA (membrane impermeant form of DHT) binds to DHT displaceable sites on the plasma membrane. Also, treatment with DHT-BSA in the C6 cells resulted in a significant decrease in phosphor-ERK and Akt levels, suggesting the existence of two different pathways through which DHT can influence the activity of these signaling pathways. With respect to cell survival, the C6 cells and primary cortical astrocytes were treated with the metabolic and oxidative insult, iodoacetic acid (IAA), in the presence or absence of DHT, DHT-BSA…
author: Gatson, John Wayne
language: en
keywords: Biology, Cell and Developmental Biology, Cell Biology, Cells, Cellular and Molecular Physiology, Life Sciences, Medical Cell Biology, Medical Neurobiology, Medical Sciences, Medicine and Health Sciences, Molecular and Cellular Neuroscience, Nervous System, Neuroscience and Neurobiology, Neurosciences, Other Cell and Developmental Biology, Membrane androgen receptor, brain, apoptotic cell death, rats, dihydrotestosterone, DHT-BSA, glioma, c6 cells, iodoacetic acid, IA, astrocytes, injury
date published: 2007-02-01
date modified: 2026-07-27T21:19:04Z
provider: Texas Digital Library
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Texas Digital Library

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property ID: Handle
value: https://hdl.handle.net/20.500.12503/29006