Progesterone regulates the phosphorylation of protein phosphatases in the brain

  title={Progesterone regulates the phosphorylation of protein phosphatases in the brain},
  author={Miguel A.R. Amorim and Christian Guerra-Araiza and Olga Pern{\'i}a and Edgar F. da Cruz e Silva and Luis Miguel Garcia-Segura},
  journal={Journal of Neuroscience Research},
Previous studies have shown that progesterone modulates the activity of different kinases and the phosphorylation of Tau in the brain. These actions of progesterone may be involved in the hormonal regulation of neuronal differentiation, neuronal function, and neuroprotection. However, the action of progesterone on protein phosphatases in the nervous system has not been explored previously. In this study we have assessed the effect of the administration of progesterone to adult ovariectomized… 
Progesterone as a regulator of phosphorylation in the central nervous system
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 andosphatase and tensin homolog deleted on chromosome 10 are reviewed.
Effect of chronic administration of estradiol, progesterone, and tibolone on the expression and phosphorylation of glycogen synthase kinase‐3β and the microtubule‐associated protein tau in the hippocampus and cerebellum of female rat
Results indicate that chronic administration of gonadal hormones and tibolone modulates tau and GSK3β phosphorylation in hippocampus and cerebellum of the rat and may exert a neuroprotective effect in these tissues.
Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice
Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes.
A novel functional interplay between Progesterone Receptor-B and PTEN, via AKT, modulates autophagy in breast cancer cells
It is reported 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.
Tau Phosphorylation in Female Neurodegeneration: Role of Estrogens, Progesterone, and Prolactin
The scope of this work is to review the existing evidence on how a set of hormones (estrogen, progesterone, and prolactin) affect tau phosphorylation in the brain of females under both physiological and pathological conditions.
Reproductive Stage and Modulation of Stress‐Induced Tau Phosphorylation in Female Rats
A steep, yet transient stress‐induced dephosphorylation of tau, influenced by GSK3, in the hippocampus of lactating rats is suggested, suggesting decreased sensitivity to stress during lactation modulates stress‐ induced tau‐P.
Therapeutic targets in Alzheimer's disease and related tauopathies.
  • C. Corbo, A. Alonso
  • Biology
    Progress in molecular biology and translational science
  • 2011
Mechanisms of Pain Modulation by Sex Hormones in Migraine
(Headache 2011;51:905‐922)
UNIVERSITY OF CALIFORNIA, SAN DIEGO Dephosphorylation of tau in lactating rats subjected to acute restraint stress A Thesis submitted in partial satisfaction of the requirements for the degree Master of Science in Biology by
  • 2014


Regulation of the phosphoinositide‐3 kinase and mitogen‐activated protein kinase signaling pathways by progesterone and its reduced metabolites in the rat brain
Progesterone metabolites partially mimicked the effect of progesterone and had a stronger effect on MAPK and PI3K signaling in the hypothalamus than in the other brain regions, suggesting that progester one regulates MAPKand PI3k signaling pathways in the central nervous system in vivo.
Role of Protein Phosphatases in Estrogen-Mediated Neuroprotection
The results suggest that 17β-estradiol may protect cells against glutamate-induced oxidative stress and excitotoxicity by activating a combination of protein phosphatases.
Ovarian hormones elicit phosphorylation of akt and extracellular-signal regulated kinase in explants of the cerebral cortex
The data offer novel mechanisms for both progesterone and estrogen action in the central nervous system, demonstrating the functional and mechanistic diversity of gonadal hormones and supporting their neuroprotective potential for such neurodegenerative disorders as Alzheimer disease.
Effects of progesterone and its reduced metabolites, dihydroprogesterone and tetrahydroprogesterone, on the expression and phosphorylation of glycogen synthase kinase‐3 and the microtubule‐associated protein Tau in the rat cerebellum
The regulation of Tau expression and phosphorylation by progesterone may contribute to the hormonal regulation of cerebellar function by the modification of neuronal cytoskeleton.
Protein phosphatase 1, protein phosphatase 2A, and calcineurin play a role in estrogen-mediated neuroprotection.
It is concluded that in the face of cytotoxic challenges in vitro and in vivo, estrogens maintain the function of PP1, PP2A, and calcineurin.
PP2A regulates tau phosphorylation directly and also indirectly via activating GSK-3beta.
It is shown that PP2A dephosphorylated tau at several phosphorylation sites with different efficiencies, and this study provides a new insight into the role ofPP2A down-regulation in neurofibrillary degeneration in AD.
Progesterone biosynthesis and action in the developing neuron.
This work presents the first demonstration of de novo neuronal neurosteroidogenesis in the brain from cholesterol, and summarizes the advances made in the understanding of progesterone formation and metabolism and actions of progestersone and its metabolite in the developing neuron.
Progesterone increases brain‐derived neuroptrophic factor expression and protects against glutamate toxicity in a mitogen‐activated protein kinase‐ and phosphoinositide‐3 kinase‐dependent manner in cerebral cortical explants
With organotypic explants of the cerebral cortex, it is found that progesterone protected against glutamate‐induced toxicity and inhibition of Trk signaling, with K252a, inhibited the protective effects of progester one, suggesting that progestersone is protective via multiple and potentially related mechanisms.
Progestin receptor subtypes in the brain: the known and the unknown.
The increasing in vitro and in vivo evidence of differential transcriptional activities and coregulator interactions between PR-A and PR-B predict that these isoforms could have distinct roles in mediating additional and/or alternate signaling pathways within steroid-sensitive neurons.