Mutagenesis of the glucocorticoid receptor in mice

Kellendonk, Christoph; Tronche, François; Reichardt, Holger M.; Schütz, Günther

doi:10.1016/s0960-0760(99)00041-2

Cited by 54 publications

(25 citation statements)

References 41 publications

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“…This distinction between direct and indirect control of gene expression by ER␣ is reminiscent of mutations in GR␣ that prevent its ability to form homodimers. In this instance, a lack of gene expression through GRE is compatible with life, whereas overall gene deletion of GR␣ is lethal (73,74). Similarly, inactivating mutations in the ER␣ gene in mice cause steroidogenesis and selective defects in reproductive and mammary tissue (71,75).…”

Section: Fig 7 Runx2 Inhibits Steroid Activitymentioning

confidence: 99%

Runx2 Integrates Estrogen Activity in Osteoblasts

McCarthy

Chang

Liu

et al. 2003

Journal of Biological Chemistry

108

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Steroids significantly effect skeletal integrity. For example, bone mass decreases with glucocorticoid excess or with estrogen depletion after menopause. Glucocorticoid suppresses gene expression by an essential skeletal tissue transcription factor, Runx2, in rat osteoblasts. We now report that estrogen enhances Runx2 activity in dose-and estrogen receptor-dependent ways independently of changes in Runx2 levels or its DNA binding potential. Estrogen receptor and Runx2 can be collected by co-immunoprecipitation. By two-hybrid gene expression analysis, high affinity complex formation involves portions of Runx2 outside of its own DNA binding domain and the DNA binding domain of the estrogen receptor. Consistent with this interaction, the stimulatory effect of estrogen on Runx2 activity is lost when the DNA binding domain of the estrogen receptor is eliminated. Unlike the stimulatory effect of estrogen and the inhibitory effect of glucocorticoid, androgen fails to increase Runx2 activity, whereas Runx2 potently suppresses gene expression induced by all three steroids. Finally, estrogen increases gene transcription by the transforming growth factor-␤ type I receptor gene promoter, which contains several Runx binding sequences, and enhances Smad dependent gene expression by transforming growth factor-␤ in osteoblasts. These results reveal that Runx2 can integrate complex effects on gene transcription in hormone-, growth factor-, and tissue-restricted ways.

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Section: Fig 7 Runx2 Inhibits Steroid Activitymentioning

confidence: 99%

Runx2 Integrates Estrogen Activity in Osteoblasts

McCarthy

Chang

Liu

et al. 2003

Journal of Biological Chemistry

108

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“…In tissue culture, lymphoid cells selected for GC resistance often show loss of, or mutant, dysfunctional GR. Thymocytes of transgenic mice with deliberately mutated GR show in vitro GC resistance (Kellendonk et al 1999;Reichardt et al 1998). Mice expressing thymus-specific antisense GR transcripts (GR-TKO mice) exhibited loss of doublenegative thymocytes, indicating the importance of GC in double-negative thymocyte survival and maturation to the DP stage (King et al 1995).…”

Section: Role Of Glucocorticoids In Thymocyte Selectionmentioning

confidence: 99%

Hormonal regulation of physiological cell turnover and apoptosis

Medh

Thompson

2000

Cell Tissue Res

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Physiological cell turnover plays an important role in maintaining normal tissue function and architecture. This is achieved by the dynamic balance of cellular regeneration and elimination, occurring periodically in tissues such as the uterus and mammary gland, or at constant rates in tissues such as the gastrointestinal tract and adipose tissue. Apoptosis has been identified as the prevalent mode of physiological cell loss in most tissues. Cell turnover is precisely regulated by the interplay of various endocrine and paracrine factors, which modulate tissue and cell-specific responses on proliferation and apoptosis, either directly, or by altering expression and function of key cell proliferative and/or death genes. Although recent studies have provided significant information on specific tissue systems, a clearly defined pathway that mediates cell turnover has not yet emerged for any tissue. Several similarities exist among the various tissues with regard to the intermediates that regulate tissue homeostasis, enabling a better understanding of the general mechanisms involved in the process. Here we review the mechanisms by which hormonal and cytokine factors mediate cell turnover in various tissues, emphasizing common themes and tissue-specific differences.

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“…The glucocorticoid receptor is a necessary tool to initiate and continue many necessary physiological processes [66] . The metabolic syndrome occurring in many people with schizophrenia, particularly those taking neuroleptics, suggests that the glucocorticoid receptor may play a role in the pathogenesis and pathophysiology of the disease.…”

Section: Future Directionsmentioning

confidence: 99%

“…The metabolic syndrome occurring in many people with schizophrenia, particularly those taking neuroleptics, suggests that the glucocorticoid receptor may play a role in the pathogenesis and pathophysiology of the disease. The development of transgenic mice with alterations of the glucocorticoid receptors may provide a tool for neuroimaging of the glucocorticoid receptor and related structures [66] .…”

Section: Future Directionsmentioning

confidence: 99%

Neurotransmitter visualization in schizophrenia

Brašić

2013

JBGC

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Background: Although the history, interview, and examination of the patient provide the foundation for the diagnosis of schizophrenia, nuclear neuroimaging investigations constitute promising tools to elucidate the pathophysiology of schizophrenia and other neuropsychiatric disorders. Imaging studies of neuroreceptors constitute research tools to investigate the role of dysfunction of the acetylcholinergic, dopaminergic, glutamatergic, serotonergic, cannabinoid, opioid, and nicotinic systems in the pathogenesis and pathophysiology of schizophrenia and related conditions.People with the phenotype of the clinical syndrome of schizophrenia likely represent multiple distinct genotypes with poorly characterized biological traits. Thus, the population of people manifesting the clinical syndrome of schizophrenia likely contains several heterogeneous biological subgroups yet to be specified.The dopamine hypothesis of schizophrenia proposes that the positive symptoms result from an excess of intrasynaptic dopamine, an excitatory neurotransmitter, and the negative symptoms result from a deficit of intrasynaptic dopamine. Accordingly, a group of people with schizophrenia likely have reduced intrasynaptic dopamine in the tonic, resting, basal state, and increased intrasynaptic dopamine in the excited, aroused, phasic state.Additionally, the glutamate hypothesis of schizophrenia suggests that dysfunction of glutamate, another excitatory neurotransmitter, in the prefrontal region results in excessive concentrations of dopamine in the striata resulting in the positive symptoms of schizophrenia. Methodology/Principal Findings:Published research about the nuclear neuroimaging techniques to identify neurotransmitters in people with schizophrenia are reviewed.Conclusions/Significance: Future research including neuronuclear imaging and genetic evaluations is needed to characterize the biological subgroups of people with the clinical syndrome of schizophrenia. Neuronuclear imaging studies will likely refine the measurement of neurotransmitters in the presynaptic, synaptic, and postsynaptic regions in people with schizophrenia and healthy people. Imaging studies of neuroreceptors during the administration of putative therapeutic agents for schizophrenia will help determine the optimal dose. In the future the research findings summarized in this article will likely be translated into clinical practice.

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Mutagenesis of the glucocorticoid receptor in mice

Cited by 54 publications

References 41 publications

Runx2 Integrates Estrogen Activity in Osteoblasts

Runx2 Integrates Estrogen Activity in Osteoblasts

Hormonal regulation of physiological cell turnover and apoptosis

Neurotransmitter visualization in schizophrenia

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