Nuclear Receptor Coactivators: Regulators of Steroid Action in Brain and Behaviour

Tetel, Marc J.; Acharya, Kalpana D.

doi:10.1111/jne.12065

Cited by 33 publications

(23 citation statements)

References 158 publications

(215 reference statements)

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“…A classical steroid genomic effect on P0 is supported by the presence of putative progesterone responsive elements on the P0 gene [53]. In further support of a classic genomic mechanism, steroid receptor coactivator (SRC)-1, a member of the p160 family of nuclear receptor coactivators [55], is involved in the control of P0 expression [56]. In further support of PR functioning with nuclear receptor coactivators, cells of the sciatic nerve of female rats co-express PR and SRC-2, another member of the p160 family (Fig.…”

Section: The Pns As a Physiological Target Of Neuroactive Steroidsmentioning

confidence: 98%

Neuroactive steroids and the peripheral nervous system: An update

et al. 2015

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In the present review we summarize observations to date supporting the concept that neuroactive steroids are synthesized in the peripheral nervous system, regulate the physiology of peripheral nerves and exert notable neuroprotective actions. Indeed, neuroactive steroids have been recently proposed as therapies for different types of peripheral neuropathy, like for instance those occurring during aging, chemotherapy, physical injury and diabetes. Moreover, pharmacological tools able to increase the synthesis of neuroactive steroids might represent new interesting therapeutic strategy to be applied in case of peripheral neuropathy.

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Section: The Pns As a Physiological Target Of Neuroactive Steroidsmentioning

confidence: 98%

Neuroactive steroids and the peripheral nervous system: An update

et al. 2015

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“…SRC-1 and SRC-2 are important in energy homeostasis, circadian rhythm, sexual differentiation of the brain, stress, and reproductive behavior ( Auger et al, 2000 ; Charlier et al, 2006 ; Molenda-Figueira et al, 2006 ; Winnay et al, 2006 ; Lachize et al, 2009 ; Zhu et al, 2013 ; Stashi et al, 2014a,b ). For example, these coactivators mediate ER and PR action in brain ( Tetel et al, 2009 ; Tetel and Acharya, 2013 ), and are highly expressed in the VMN, ARC, MPA, hippocampus, and amygdala ( Meijer et al, 2000 ; Tetel et al, 2007 ; Bian et al, 2011 ; Tognoni et al, 2011 ). The majority of 17β-estradiol benzoate (EB)-induced PR cells in the VMN, ARC, and MPA of female mice express both SRC-1 and SRC-2 ( Tognoni et al, 2011 ), suggesting that these cells are functional sites of interaction between steroid receptors and coactivators in brain.…”

Section: Introductionmentioning

confidence: 99%

Estradiol Preferentially Induces Progestin Receptor-A (PR-A) Over PR-B in Cells Expressing Nuclear Receptor Coactivators in the Female Mouse Hypothalamus

Acharya

Finkelstein

Bless

et al. 2015

eneuro

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Estrogens act in brain to profoundly influence neurogenesis, sexual differentiation, neuroprotection, cognition, energy homeostasis, and female reproductive behavior and physiology through a variety of mechanisms, including the induction of progestin receptors (PRs). PRs are expressed as two isoforms, PR-A and PR-B, that have distinct functions in physiology and behavior. Because these PR isoforms cannot be distinguished using cellular resolution techniques, the present study used isoform-specific null mutant mice that lack PR-A or PR-B for the first time to investigate whether 17β-estradiol benzoate (EB) regulates the differential expression of the PR isoforms in the ventromedial nucleus of the hypothalamus (VMN), arcuate nucleus, and medial preoptic area, brain regions that are rich in EB-induced PRs. Interestingly, EB induced more PR-A than PR-B in all three brain regions, suggesting that PR-A is the predominant isoform in these regions. Given that steroid receptor coactivator (SRC)-1 and SRC-2 are important in estrogen receptor (ER)-dependent transcription in brain, including PR induction, we tested whether the expression of these coactivators was correlated with PR isoform expression. The majority of EB-induced PR cells expressed both SRC-1 and SRC-2 in the three brain regions of all genotypes. Interestingly, the intensity of PR-A immunoreactivity correlated with SRC-2 expression in the VMN, providing a potential mechanism for selective ER-mediated transactivation of PR-A over PR-B in a brain region-specific manner. In summary, these novel findings indicate that estrogens differentially regulate PR-A and PR-B expression in the female hypothalamus, and provide a mechanism by which steroid action in brain can selectively modulate behavior and physiology.

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“…a constitutively active and a ligand-dependent function located at the amino-terminus and in the carboxy-terminal ligand-binding domain of ERs, respectively [44]. The DNA-bound dimers recruit co-regulator proteins [45], which can participate in and also recruit many enzymatic and structural proteins permitting the modulation of chromatin structure to facilitate or block gene expression [46]. Additionally, ERE-independent mechanisms have also been shown [47].…”

Section: Genomic Pathways In E2 Neuroprotectionmentioning

confidence: 99%

17β-Estradiol as a Neuroprotective Agent

Prókai-Tátrai¹,

Prókai²

2018

Sex Hormones in Neurodegenerative Processes and Diseases

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The pathophysiology of neurodegeneration in the central nervous system is complex and multifactorial in nature and yet to be fully understood. Broad-spectrum neuroprotective agents with multiple mechanisms of action rather than a single druggable target are, therefore, highly desirable. The main human estrogen, 17β-estradiol, can also be considered a neurosteroid as it forms de novo in the central nervous system, and it possesses beneficial effects against practically all critical contributors to neurodegeneration to collectively thwart both the initiation and the progression of neuronal cell death. This chapter details the main aspects of the hormone's genomic and non-genomic actions important to protect the highly vulnerably neurons of the central nervous system, as well as translational efforts to successfully realize its powerful neuroprotective potential in clinical setting while ensuring both therapeutic safety and efficacy.

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Nuclear Receptor Coactivators: Regulators of Steroid Action in Brain and Behaviour

Cited by 33 publications

References 158 publications

Neuroactive steroids and the peripheral nervous system: An update

Neuroactive steroids and the peripheral nervous system: An update

Estradiol Preferentially Induces Progestin Receptor-A (PR-A) Over PR-B in Cells Expressing Nuclear Receptor Coactivators in the Female Mouse Hypothalamus

17β-Estradiol as a Neuroprotective Agent

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