scholarly journals Progesterone Increases the Release of Brain-Derived Neurotrophic Factor from Glia via Progesterone Receptor Membrane Component 1 (Pgrmc1)-Dependent ERK5 Signaling

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4389-4400 ◽  
Author(s):  
Chang Su ◽  
Rebecca L. Cunningham ◽  
Nataliya Rybalchenko ◽  
Meharvan Singh
Keyword(s):  
Progesterone Receptor ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Experimental Models ◽  
Protective Effects ◽  
Membrane Component ◽  
Signaling Mechanism ◽  
Receptor Membrane ◽  
Bdnf Signaling

Progesterone (P4) is cytoprotective in various experimental models, but our understanding of the mechanisms involved is still incomplete. Our laboratory has implicated brain-derived neurotrophic factor (BDNF) signaling as an important mediator of P4's protective actions. We have shown that P4 increases the expression of BDNF, an effect mediated by the classical P4 receptor (PR), and that the protective effects of P4 were abolished using inhibitors of Trk receptor signaling. In an effort to extend our understanding of the interrelationship between P4 and BDNF signaling, we determined whether P4 influenced BDNF release and examined the role of the classical PR and a putative membrane PR, progesterone receptor membrane component-1 (Pgrmc1), as mediators of this response. Given recent data from our laboratory that supported the role of ERK5 in BDNF release, we also tested whether P4-induced BDNF release was mediated by ERK5. In this study, we found that P4 and the membrane-impermeable P4 (P4-BSA) both induced BDNF release from cultured C6 glial cells and primary astrocytes. Both these cells lack the classical nuclear/intracellular PR but express high levels of membrane-associated PR, including Pgrmc1. Using RNA interference-mediated knockdown of Pgrmc1 expression, we determined that P4-induced BDNF release was dependent on the expression of Pgrmc1, although pharmacological inhibition of the PR failed to alter the effects of P4. Furthermore, the BDNF release elicited by P4 was mediated by ERK5, and not ERK1/2. Collectively, our data describe that P4 elicits an increase in BDNF release from glia via a Pgrmc1-induced ERK5 signaling mechanism and identify Pgrmc1 as a potential therapeutic target for future hormone-based drug development for the treatment of such degenerative diseases as Alzheimer's disease as well as other diseases wherein neurotrophin dysregulation is noted.

scholarly journals TrkB-Mediated Neuroprotective and Antihypoxic Properties of Brain-Derived Neurotrophic Factor

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Maria V. Vedunova ◽  
Tatiana A. Mishchenko ◽  
Elena V. Mitroshina ◽  
Irina V. Mukhina
Keyword(s):  
Neurotrophic Factor ◽  
Acute Hypoxia ◽  
Brain Derived Neurotrophic Factor ◽  
Bioelectrical Activity ◽  
Multielectrode Arrays ◽  
Protective Effects ◽  
Hippocampal Cultures ◽  
Tropomyosin Related Kinase B ◽  
Posthypoxic Period

The neuroprotective and antihypoxic effects of brain-derived neurotrophic factor (BDNF) on dissociated hippocampal cultures in a hypoxia model were investigated. These experiments demonstrate that 10 minutes of normobaric hypoxia increased the number of dead cells in primary culture, whereas a preventive application of BDNF increased the number of viable cells. Spontaneous bioelectrical and calcium activity in neural networks was analyzed using multielectrode arrays and functional intravital calcium imaging. The results indicate that BDNF affects the functional parameters of neuronal networks in dissociated hippocampal cultures over the 7-day posthypoxic period. In addition, the effects of k252a, an antagonist of tropomyosin-related kinase B (TrkB), on functional bioelectrical activity during and after acute hypoxia were investigated. It was shown that the protective effects of BDNF are associated with binding to the TrkB receptor. Finally, intravital fluorescent mRNA probes were used to study the role of NF-κB1 in the protective effects of BDNF. Our experiments revealed that BDNF application stimulates NF-κB1 mRNA synthesis in primary dissociated hippocampal cells under normal conditions but not in hypoxic state.

Regulation and role of Progesterone receptor membrane component 1 (PGRMC1) in endometrial stromal cell decidualization

Placenta ◽  
2019 ◽  
Vol 87 ◽  
pp. 69
Author(s):  
Atuya Tsuru ◽  
Mikihiro Yoshie ◽  
Ryo Yonekawa ◽  
Junya Kojima ◽  
Hirotaka Nishi ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Stromal Cell ◽  
Endometrial Stromal Cell ◽  
Membrane Component ◽  
Receptor Membrane

The emerging role of progesterone receptor membrane component 1 (PGRMC1) in cancer biology

2016 ◽  
Vol 1866 (2) ◽  
pp. 339-349 ◽  
Author(s):  
Michael A. Cahill ◽  
Jalal A. Jazayeri ◽  
Susan M. Catalano ◽  
Shinya Toyokuni ◽  
Zaklina Kovacevic ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Cancer Biology ◽  
Membrane Component ◽  
Receptor Membrane

Role of Progesterone Receptor Membrane Component-1 (PGRMC-1) on Bovine Oocyte Maturation.

2009 ◽  
Vol 81 (Suppl_1) ◽  
pp. 278-278
Author(s):  
Alberto M. Luciano ◽  
Valentina Lodde ◽  
Federica Franciosi ◽  
Fabrizio Ceciliani ◽  
John J. Peluso
Keyword(s):  
Progesterone Receptor ◽  
Oocyte Maturation ◽  
Bovine Oocyte ◽  
Membrane Component ◽  
Receptor Membrane

scholarly journals Progesterone increases blood glucose via hepatic progesterone receptor membrane component 1 under limited or impaired action of insulin

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sang R. Lee ◽  
Woo-Young Choi ◽  
Jun H. Heo ◽  
Jiyoung Huh ◽  
Globinna Kim ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Cyclic Amp ◽  
Progesterone Receptor ◽  
Insulin Action ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Membrane Component ◽  
Receptor Membrane ◽  
Hep3b Cells

Abstract Hepatic gluconeogenesis is the main pathway for blood glucose maintenance activated during fasting. Retardation of insulin action, such as in diabetes mellitus, activates gluconeogenesis during the fed state. While the role of progesterone (P4) in diabetes is controversial, the P4 receptor, progesterone receptor membrane component 1 (PGRMC1), is known to stimulate pancreatic insulin secretion. We investigated the role of P4, via hepatic PGRMC1, during gluconeogenesis. The PGRMC1 binding chemical, AG-205, induced PGRMC1 monomer (25 kDa) abundance, and increased PEPCK expression and glucose production in parallel with cyclic AMP (cAMP) induction in Hep3B cells. PGRMC1-mediated cyclic AMP was inhibited by an adenylate cyclase inhibitor (MDL-12,330A). PEPCK suppression in Pgrmc1 KO hepatocyte was not observed after treatment of MDL-12,330A. PGRMC1 knockdown or overexpression systems in Hep3B cells confirmed that PGRMC1 mediates PEPCK expression via phosphorylation of cAMP-response element binding protein (CREB). CREB phosphorylation and PEPCK expression in primary hepatocytes were greater than that in PGRMC1 knock-out hepatocytes. Progesterone increased PGRMC1 expression, which induced cAMP and PEPCK induction and glucose production. In vivo, P4 suppressed gluconeogenesis following plasma insulin induction under normal conditions in a mouse model. However, P4 increased blood glucose via gluconeogenesis in parallel with increases in PGRMC1 and PEPCK expression in mice in both insulin-deficient and insulin-resistant conditions. We conclude that P4 increases hepatic glucose production via PGRMC1, which may exacerbate hyperglycaemia in diabetes where insulin action is limited.

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