Expression and function of nuclear receptor coregulators in brain: understanding the cell-specific effects of glucocorticoids

Leiden Repository

Expression and function of nuclear receptor coregulators in brain: understanding the cell-specific effects of glucocorticoids

Type: Doctoral Thesis
Title: Expression and function of nuclear receptor coregulators in brain: understanding the cell-specific effects of glucocorticoids
Author: Laan, Siem van der
Publisher: Medical pharmacology, Leiden/Amsterdam Centre for Drug Research
Faculty of Science, Leiden University
Issue Date: 2008-11-06
Keywords: Brain
CRH
Glucocorticoids
GR
MR
N-CoR
PVN
SMRT
SRC1
Stress
Abstract: Currently, the raising awareness of the role of glucocorticoids in the onset of numerous (neuro)-pathologies constitutes the increasing necessity of understanding the mechanisms of action of glucocorticoids in bodily processes and brain functioning. Glucocorticoids mediate their effects by binding to intracellular receptors which act as transcription factors. A remarkable and yet unexplained phenomenon described more than two decades ago, is the cell-specific effects glucocorticoids bring about on gene expression in brain. For example, while glucocorticoids suppress corticotrophin-releasing hormone (CRH) synthesis in the hypothalamus, production of CRH in the central nucleus of the amygdala (CeA) is stimulated by increased hormone levels. Inasmuch as the neuroanatomical distribution of the corticosteroid receptors does not satisfactorily explain these effects, it is of interest to decipher the role of recently discovered coregu lator proteins that modulate the direction and the magnitude of steroid receptor-driven transcription. Therefore, in the current thesis the expression and function of central coregulators was studied: the coactivators SRC1a and SRC1e along with the corepressors N-CoR and SMRT were found to be expressed in brain and involved in regulation of CRH gene expression. Finally, a method that allows detection of coregulator recruitment by steroid receptors in brain tissue was developed.
Description: Promotor: E.R. de Kloet, Co-promotor: O.C. Meijer
With summary in Dutch
Faculty:
Citation: Laan, S. van der, 2008, Doctoral thesis, Leiden University
ISBN: 9789064642944
Handle: http://hdl.handle.net/1887/13221
 

Files in this item

Description Size View
application/pdf Full text 11.44Mb View/Open
application/pdf Cover 1.784Mb View/Open
application/pdf Title page_Contents 52.87Kb View/Open
application/pdf Chapter 1 483.1Kb View/Open
application/pdf Chapter 2 966.8Kb View/Open Full text at publisher site
application/pdf Chapter 3 128.2Kb View/Open Full text at publisher site
application/pdf Chapter 4 289.6Kb View/Open
application/pdf Chapter 5 472.4Kb View/Open Full text at publisher site
application/pdf Chapter 6 326.6Kb View/Open
application/pdf Chapter 7 43.81Kb View/Open
application/pdf Chapter 8 45.77Kb View/Open
application/pdf Publications_Curriculum vitae 44.62Kb View/Open
application/pdf Colour images_Afterwoord 875.1Kb View/Open
application/pdf Propositions 170.6Kb View/Open

This item appears in the following Collection(s)