Progesterone regulates the phosphorylation of protein phosphatases in the brain

Amorim, Miguel A.R.; Guerra‐Araiza, Christian; Pernía, Olga; Silva, Edgar F. da Cruz e; Garcia-Segura, Luis Miguel

doi:10.1002/jnr.22442

Cited by 11 publications

(11 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The actions of PROG during physiological conditions involve the regulation of the activity of different kinases and phosphatases (Amorim et al, 2010;Frye and Walf, 2008;Guerra-Araiza et al, 2007Mani and Oyola, 2012) and the activation of membrane and intracellular progesterone receptors Mani and Oyola, 2012;Meffre et al, 2013). PROG and its metabolite DHP bind to intracellular PROG receptors , which are expressed in the nervous system (Guerra-Araiza et al, 2003).…”

Section: Physiological Actions Of Progesterone and Its Metabolites Inmentioning

confidence: 99%

Levels and actions of progesterone and its metabolites in the nervous system during physiological and pathological conditions

Melcangi

Giatti

Calabrese

et al. 2014

Progress in Neurobiology

114

View full text Add to dashboard Cite

Progesterone is synthesized and actively metabolized in the central and peripheral nervous system, into neuroactive steroid metabolites, such as dihydroprogesterone, allopregnanolone and isopregnanolone. Progesterone and/or its metabolites exert a variety of effects acting as physiological regulators of neuronal and glial development and plasticity, controlling reproduction, neuroendocrine events, mood and affection. In addition, these neuroactive steroids maintain neural homeostasis and exert neuroprotective actions. In agreement, metabolic pathways of progesterone are affected by modifications in the level of gonadal hormones and by pathology or injury with a regional specificity and in a sex-dimorphic way. Therefore, observations here summarized may provide a background to design sex-specific therapies based on progesterone metabolites. On this point of view, considering that one of the major limits of a therapy based on neuroactive steroids could be modifications in their plasma levels and their consequent peripheral effects, pharmacological treatments aimed to increase their levels in the nervous system could provide an interesting therapeutic option.

show abstract

Section: Physiological Actions Of Progesterone and Its Metabolites Inmentioning

confidence: 99%

Levels and actions of progesterone and its metabolites in the nervous system during physiological and pathological conditions

Melcangi

Giatti

Calabrese

et al. 2014

Progress in Neurobiology

114

View full text Add to dashboard Cite

show abstract

“…Recently it has been reported that, in rat brain, progesterone regulates the expression of Phosphatase and Tensin homolog deleted on chromosome TEN (PTEN) gene . PTEN acts as a tumour suppressor by dephosphorylating the plasma membrane lipid second messenger phosphoinositide‐3,4,5‐trisphosphate (PIP3) antagonizing signal transduction downstream of phosphatidylinositol‐3 kinase (PI3K) and suppressing cell growth and survival .…”

Section: Introductionmentioning

confidence: 99%

A novel functional interplay between Progesterone Receptor‐B and PTEN, via AKT, modulates autophagy in breast cancer cells

Amicis

Guido

Santoro

et al. 2014

J Cellular Molecular Medi

View full text Add to dashboard Cite

The tumour suppressor activity of the phosphatase and tensin homologue on chromosome 10 (PTEN) is subject of intense investigative efforts, although limited information on its regulation in breast cancer is available. Herein, we report that, in breast cancer cells, progesterone (OHPg), through its cognate receptor PR-B, positively modulates PTEN expression by inducing its mRNA and protein levels, and increasing PTEN-promoter activity. The OHPg-dependent up-regulation of PTEN gene activity requires binding of the PR-B to an Sp1-rich region within the PTEN gene promoter. Indeed, ChIP and EMSA analyses showed that OHPg treatment induced the occupancy of PTEN promoter by PR and Sp1 together with transcriptional coactivators such as SRC1 and CBP. PR-B isoform knockdown abolished the complex formation indicating its specific involvement. The OHPg/PR-B dependent induction of PTEN causes the down-regulation of PI3K/AKT signal, switching on the autophagy process through an enhanced expression of UVRAG and leading to a reduced cell survival. Altogether these findings highlight a novel functional connection between OHPg/PR-B and tumour suppressor pathways in breast cancer.

show abstract

“…Nongenomic effects of progesterone on DRG neurons include potentiating P2X2 receptors 88 . Progesterone also regulates activity of kinases and phosphatases, 89 and activates MAP kinases including ERK 90 . Little is known about potential effects of progesterone on central or peripheral trigeminal neurons, or about how estrogen and progesterone may interact to regulate ERK activation.…”

mentioning

confidence: 99%

Mechanisms of Pain Modulation by Sex Hormones in Migraine

et al. 2011

View full text Add to dashboard Cite

A number of pain conditions, acute as well as chronic, are much more prevalent in women, such as temporomandibular disorder (TMD), irritable bowel syndrome, fibromyalgia, and migraine. The association of female sex steroids with these nociceptive conditions is well known, but the mechanisms of their effects on pain signaling are yet to be deciphered. We reviewed the mechanisms through which female sex steroids might influence the trigeminal nociceptive pathways with a focus on migraine. Sex steroid receptors are located in trigeminal circuits, providing the molecular substrate for direct effects. In addition to classical genomic effects, sex steroids exert rapid nongenomic actions to modulate nociceptive signaling. Although there are only a handful of studies that have directly addressed the effect of sex hormones in animal models of migraine, the putative mechanisms can be extrapolated from observations in animal models of other trigeminal pain disorders, like TMD. Sex hormones may regulate sensitization of trigeminal neurons by modulating expression of nociceptive mediator such as calcitonin gene-related peptide. Its expression is mostly positively regulated by estrogen, although a few studies also report an inverse relationship. Serotonin (5-Hydroxytryptamine [5-HT]) is a neurotransmitter implicated in migraine; its synthesis is enhanced in most parts of brain by estrogen, which increases expression of the rate-limiting enzyme tryptophan hydroxylase and decreases expression of the serotonin re-uptake transporter. Downstream signaling, including extracellular signal-regulated kinase activation, calcium-dependent mechanisms, and cAMP response element-binding activation, are thought to be the major signaling events affected by sex hormones. These findings need to be confirmed in migraine-specific animal models that may also provide clues to additional ion channels, neuropeptides, and intracellular signaling cascades that contribute to the increased prevalence of migraine in women.

show abstract

Progesterone regulates the phosphorylation of protein phosphatases in the brain

Cited by 11 publications

References 66 publications

Levels and actions of progesterone and its metabolites in the nervous system during physiological and pathological conditions

Levels and actions of progesterone and its metabolites in the nervous system during physiological and pathological conditions

A novel functional interplay between Progesterone Receptor‐B and PTEN, via AKT, modulates autophagy in breast cancer cells

Mechanisms of Pain Modulation by Sex Hormones in Migraine

Contact Info

Product

Resources

About