scholarly journals Progesterone Activates a Progesterone Receptor Membrane Component 1-Dependent Mechanism That Promotes Human Granulosa/Luteal Cell Survival But Not Progesterone Secretion

2009 ◽  
Vol 23 (7) ◽  
pp. 1124-1125
Author(s):  
John J. Peluso ◽  
Xiufang Liu ◽  
Anna Gawkowska ◽  
Erika Johnston-MacAnanny
Keyword(s):  
Progesterone Receptor ◽  
Cell Survival ◽  
Luteal Cell ◽  
Membrane Component ◽  
Progesterone Secretion ◽  
Receptor Membrane ◽  
Dependent Mechanism

scholarly journals Progesterone Activates a Progesterone Receptor Membrane Component 1-Dependent Mechanism That Promotes Human Granulosa/Luteal Cell Survival But Not Progesterone Secretion

2009 ◽  
Vol 94 (7) ◽  
pp. 2644-2649 ◽  
Author(s):  
John J. Peluso ◽  
Xiufang Liu ◽  
Anna Gawkowska ◽  
Erika Johnston-MacAnanny
Keyword(s):  
Progesterone Receptor ◽  
Binding Proteins ◽  
In Vitro Studies ◽  
Fertility Treatment ◽  
Luteal Cell ◽  
Membrane Component ◽  
Binding Studies ◽  
Dapi Staining ◽  
Receptor Membrane

Context: Progesterone (P4) promotes its own secretion and the survival of human granulosa/luteal (GL) cells. Objective: The objective of these studies was to determine whether progesterone receptor membrane component-1 (PGRMC1) mediates P4’s actions. Design: In vitro studies were conducted on GL cells from women undergoing in vitro fertilization and GL5 cells, which are derived from GL cells. Setting and Patients: GL cells were obtained from women undergoing fertility treatment at a university-based clinic and used for in vitro studies. Main Outcome Measures: PCR, Western blot, and immunocytochemistry were used to detect various progestin binding proteins. 3H-P4 binding kinetics were assessed on partially purified PGRMC1. Apoptosis was determined after culture by either TUNEL or DAPI staining. P4 was measured by an ELISA assay. PGRMC1 was depleted using small interfering RNA. Results: GL and GL5 cells expressed several P4 binding proteins including the nuclear progesterone receptor (PGR), progestin/adipoQ receptors (PAQR 7, 8, and 5) and PGRMC1. Ligand binding studies revealed that both P4 and the progestin, R5020, bound PGRMC1 with an EC50 of approximately 10 nm. Interestingly, P4 inhibited apoptosis at concentrations in the 10 nm range, whereas R5020 stimulated P4 secretion at concentrations of at lease 16 μm. Depleting PGRMC1 attenuated P4’s antiapoptotic action but failed to influence R5020-induced P4 secretion. Conclusions: These studies conclusively demonstrate that in human GL cells PGRMC1 functions as a receptor through which P4 activates a signal cascade that prevents apoptosis. In contrast, PGRMC1 does not mediate P4’s ability to acutely promote its own secretion.

scholarly journals Glycyrrhizin Derivatives Suppress Cancer Chemoresistance by Inhibiting Progesterone Receptor Membrane Component 1

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3265
Author(s):  
Yasuaki Kabe ◽  
Ikko Koike ◽  
Tatsuya Yamamoto ◽  
Miwa Hirai ◽  
Ayaka Kanai ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Cancer Progression ◽  
Egf Receptor ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Human Colon ◽  
Titration Calorimetry ◽  
Membrane Component ◽  
Human Colon Cancer ◽  
Receptor Membrane

Progesterone receptor membrane component 1 (PGRMC1) is highly expressed in various cancer cells and contributes to tumor progression. We have previously shown that PGRMC1 forms a unique heme-stacking functional dimer to enhance EGF receptor (EGFR) activity required for cancer proliferation and chemoresistance, and the dimer dissociates by carbon monoxide to attenuate its biological actions. Here, we determined that glycyrrhizin (GL), which is conventionally used to ameliorate inflammation, specifically binds to heme-dimerized PGRMC1. Binding analyses using isothermal titration calorimetry revealed that some GL derivatives, including its glucoside-derivative (GlucoGL), bind to PGRMC1 potently, whereas its aglycone, glycyrrhetinic acid (GA), does not bind. GL and GlucoGL inhibit the interaction between PGRMC1 and EGFR, thereby suppressing EGFR-mediated signaling required for cancer progression. GL and GlucoGL significantly enhanced EGFR inhibitor erlotinib- or cisplatin (CDDP)-induced cell death in human colon cancer HCT116 cells. In addition, GL derivatives suppressed the intracellular uptake of low-density lipoprotein (LDL) by inhibiting the interaction between PGRMC1 and the LDL receptor (LDLR). Effects on other pathways cannot be excluded. Treatment with GlucoGL and CDDP significantly suppressed tumor growth following xenograft transplantation in mice. Collectively, this study indicates that GL derivatives are novel inhibitors of PGRMC1 that suppress cancer progression, and our findings provide new insights for cancer treatment.

Progesterone receptor membrane component 1 (PGRMC1) expression in canine mammary tumors: A preliminary study

2020 ◽  
Vol 132 ◽  
pp. 101-107
Author(s):  
Laura Terzaghi ◽  
Barbara Banco ◽  
Debora Groppetti ◽  
Priscila C. Dall'Acqua ◽  
Chiara Giudice ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Mammary Tumors ◽  
Membrane Component ◽  
Canine Mammary Tumors ◽  
Receptor Membrane ◽  
Preliminary Study

scholarly journals Progesterone receptor membrane component 1 reduces cardiac steatosis and lipotoxicity via activation of fatty acid oxidation and mitochondrial respiration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sang R. Lee ◽  
Jun H. Heo ◽  
Seong Lae Jo ◽  
Globinna Kim ◽  
Su Jung Kim ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Progesterone Receptor ◽  
Fatty Acid Oxidation ◽  
Mitochondrial Respiration ◽  
De Novo Lipogenesis ◽  
Acid Oxidation ◽  
Membrane Component ◽  
Markers Of Inflammation ◽  
Receptor Membrane

AbstractObesity is implicated in cardiovascular disease and heart failure. When fatty acids are transported to and not adequately oxidized in cardiac cells, they accumulate, causing lipotoxicity in the heart. Since hepatic progesterone receptor membrane component 1 (Pgrmc1) suppressed de novo lipogenesis in a previous study, it was questioned whether cardiac Pgrmc1 protects against lipotoxicity. Hence, we focused on the role of cardiac Pgrmc1 in basal (Resting), glucose-dominant (Refed) and lipid-dominant high-fat diet (HFD) conditions. Pgrmc1 KO mice showed high FFA levels and low glucose levels compared to wild-type (WT) mice. Pgrmc1 KO mice presented low number of mitochondrial DNA copies in heart, and it was concomitantly observed with low expression of TCA cycle genes and oxidative phosphorylation genes. Pgrmc1 absence in heart presented low fatty acid oxidation activity in all conditions, but the production of acetyl-CoA and ATP was in pronounced suppression only in HFD condition. Furthermore, HFD Pgrmc1 KO mice resulted in high cardiac fatty acyl-CoA levels and TG level. Accordingly, HFD Pgrmc1 KO mice were prone to cardiac lipotoxicity, featuring high levels in markers of inflammation, endoplasmic reticulum stress, oxidative stress, fibrosis, and heart failure. In vitro study, it was also confirmed that Pgrmc1 enhances rates of mitochondrial respiration and fatty acid oxidation. This study is clinically important because mitochondrial defects in Pgrmc1 KO mice hearts represent the late phase of cardiac failure.

scholarly journals Roles of Progesterone Receptor Membrane Component 1 in Oxidative Stress–Induced Aging in Chorion Cells

2018 ◽  
Vol 26 (3) ◽  
pp. 394-403 ◽  
Author(s):  
Liping Feng ◽  
Terrence K. Allen ◽  
William P. Marinello ◽  
Amy P. Murtha
Keyword(s):  
Oxidative Stress ◽  
Progesterone Receptor ◽  
Membrane Component ◽  
Receptor Membrane
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