Progestin Receptor Subtypes in the Brain: The Known and the Unknown

Mani, Shaila K.

doi:10.1210/en.2008-0097

Cited by 47 publications

(30 citation statements)

References 82 publications

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“…Progesterone elicits its effects via progesterone receptors (PRs), which include classical nuclear PRs (two major isoforms PR-A and PR-B) and recently recognized membrane PRs [3], [5], [6], [7]. The classical mechanism of progesterone action is mediated by nuclear PRs, which function as transcription factors by binding to specific progesterone response elements within the promoter region of target genes to modulate transcription and genomic networks [3], [4], [8].…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Effects of Progesterone in Lipopolysaccharide-Stimulated BV-2 Microglia

et al. 2014

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Female sex is associated with improved outcome in experimental brain injury models, such as traumatic brain injury, ischemic stroke, and intracerebral hemorrhage. This implies female gonadal steroids may be neuroprotective. A mechanism for this may involve modulation of post-injury neuroinflammation. As the resident immunomodulatory cells in central nervous system, microglia are activated during acute brain injury and produce inflammatory mediators which contribute to secondary injury including proinflammatory cytokines, and nitric oxide (NO) and prostaglandin E2 (PGE2), mediated by inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively. We hypothesized that female gonadal steroids reduce microglia mediated neuroinflammation. In this study, the progesterone’s effects on tumor necrosis factor alpha (TNF-α), iNOS, and COX-2 expression were investigated in lipopolysaccharide (LPS)-stimulated BV-2 microglia. Further, investigation included nuclear factor kappa B (NF-κB) and mitogen activated protein kinase (MAPK) pathways. LPS (30 ng/ml) upregulated TNF-α, iNOS, and COX-2 protein expression in BV-2 cells. Progesterone pretreatment attenuated LPS-stimulated TNF-α, iNOS, and COX-2 expression in a dose-dependent fashion. Progesterone suppressed LPS-induced NF-κB activation by decreasing inhibitory κBα and NF-κB p65 phosphorylation and p65 nuclear translocation. Progesterone decreased LPS-mediated phosphorylation of p38, c-Jun N-terminal kinase and extracellular regulated kinase MAPKs. These progesterone effects were inhibited by its antagonist mifepristone. In conclusion, progesterone exhibits pleiotropic anti-inflammatory effects in LPS-stimulated BV-2 microglia by down-regulating proinflammatory mediators corresponding to suppression of NF-κB and MAPK activation. This suggests progesterone may be used as a potential neurotherapeutic to treat inflammatory components of acute brain injury.

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Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Effects of Progesterone in Lipopolysaccharide-Stimulated BV-2 Microglia

et al. 2014

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“…PR is also expressed by variety cell types in different regions of the central nervous system. Growing evidence suggest that the hormone controls reproductive behavior and several other nonreproductive functions in the central nervous system as reviewed in (Brinton et al, 2008;Mani, 2008).…”

Section: Progesterone Signaling In Non-reproductive Tissuesmentioning

confidence: 99%

Paracrine signaling by progesterone

Rajaram

Brisken

2012

Molecular and Cellular Endocrinology

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a b s t r a c tSteroid hormones coordinate and control the development and function of many organs and are implicated in many pathological processes. Progesterone signaling, in particular, is essential for several important female reproductive functions. Physiological effects of progesterone are mediated by its cognate receptor, expressed in a subset of cells in target tissues. Experimental evidence has accumulated that progesterone acts through both cell intrinsic as well as paracrine signaling mechanisms. By relegating the hormonal stimulus to paracrine signaling cascades the systemic signal gets amplified locally and signaling reaches different cell types that are devoid of hormone receptors. Interestingly, distinct biological responses to progesterone in different target tissues rely on several tissue-specific and some common paracrine factors that coordinate biological responses in different cell types. Evidence is forthcoming that the intercellular signaling pathways that control development and physiological functions are important in tumorigenesis.Crown Copyright Ó 2011 Published by Elsevier Ireland Ltd. All rights reserved. Abbreviations: ADAM8, a disintegrin and metalloproteinase 8; ADAMTS-1, a disintegrin and metalloproteinase with thrombospondin motif-1; BrdU, bromodeoxyuridine;

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“…It is known that classical progesterone receptors control the actions exerted by the hormone and by its metabolite DHP in the brain (23,37). Classical progesterone receptors are located intracellularly and are able to modulate the expression of genes that have progesterone response elements in their promoters (38).…”

Section: Nuclear-initiated and Membrane-initiated Progesterone Signalmentioning

confidence: 99%

Progesterone as a regulator of phosphorylation in the central nervous system

Amorim¹,

Guerra‐Araiza

Garcia-Segura

2010

Hormone Molecular Biology and Clinical Investigation

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Progesterone exerts a variety of actions in the central nervous system under physiological and pathological conditions. As in other tissues, progesterone acts in the brain through classical progesterone receptors and through alternative mechanisms. Here, we review the role of progesterone as a regulator of kinases and phosphatases, such as extracellular-signal regulated kinases, phosphoinositide 3-kinase, Akt, glycogen synthase kinase 3, protein phosphatase 2A and phosphatase and tensin homolog deleted on chromosome 10. In addition, we analyzed the effects of progesterone on the phosphorylation of Tau, a protein that is involved in microtubule stabilization in neurons.

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Progestin Receptor Subtypes in the Brain: The Known and the Unknown

Cited by 47 publications

References 82 publications

Anti-Inflammatory Effects of Progesterone in Lipopolysaccharide-Stimulated BV-2 Microglia

Anti-Inflammatory Effects of Progesterone in Lipopolysaccharide-Stimulated BV-2 Microglia

Paracrine signaling by progesterone

Progesterone as a regulator of phosphorylation in the central nervous system

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