scholarly journals Expression of membrane progesterone receptors on human T lymphocytes and Jurkat cells and activation of G-proteins by progesterone

2007 ◽  
Vol 196 (1) ◽  
pp. 67-77 ◽  
Author(s):  
C Dosiou ◽  
A E Hamilton ◽  
Y Pang ◽  
M T Overgaard ◽  
S Tulac ◽  
...  

Although there is significant evidence for progesterone's role as an immunomodulator, nuclear progesterone receptors have not been consistently identified in immune cells. Recently, three new putative membrane progesterone receptors (mPRs), mPRα, mPRβ, and mPRγ have been described. The objective of this study was to examine whether mPRs are expressed in peripheral blood leukocytes (PBLs) in women of reproductive age, and to further characterize them in T lymphocytes and immortalized T cells (Jurkat cells). Transcripts for mPRα and mPRβ but not mPRγ, were detected by RT-PCR in PBLs, T lymphocytes, and Jurkat cells. Western blot analysis showed the presence of the mPRα and mPRβ proteins on cell membranes of T lymphocytes and Jurkat cells. Expression of the mPRα mRNA was upregulated in the luteal phase of the menstrual cycle in cluster of differentiation (CD)8+, but not in CD4+, T lymphocytes. Radioreceptor assays revealed specific [3H]progesterone binding to T- and Jurkat cell membranes (Kd 4.25 nM) characteristic of steroid membrane receptors. Progesterone activated an inhibitory G-protein (Gi), suggesting that mPRs are coupled to Gi in Jurkat cells. These results suggest a potential novel mechanism for progesterone's immunoregulatory function through activation of mPRs.

2019 ◽  
Vol 72 ◽  
pp. 55-61
Author(s):  
Mitra Rafiee ◽  
Mohsen Naseri ◽  
Maryam Akbari-Fakhrabadi ◽  
Narges Motamedi ◽  
Ataollah Ghahiri ◽  
...  

2007 ◽  
Vol 77 (Suppl_1) ◽  
pp. 123-123
Author(s):  
Kalidou Ndiaye ◽  
Daniel Poole ◽  
Joy Pate

2012 ◽  
Vol 40 (1) ◽  
pp. 200-204 ◽  
Author(s):  
Patricia Moussatche ◽  
Thomas J. Lyons

The steroid hormone progesterone regulates many critical aspects of vertebrate physiology. The nuclear receptor for progesterone functions as a ligand-activated transcription factor, directly regulating gene expression. This type of signalling is referred to as the ‘genomic’ pathway. Nevertheless, progesterone also stimulates rapid physiological effects that are independent of transcription. This pathway, termed ‘non-genomic’, is mediated by the mPRs (membrane progesterone receptors). These mPRs belong to a larger class of membrane receptors called PAQRs (progestin and adipoQ receptors), which include receptors for adiponectin in vertebrates and osmotin in fungi. mPRs have been shown to activate inhibitory G-proteins, suggesting that they act as GPCRs (G-protein-coupled receptors). However, PAQRs do not resemble GPCRs with respect to topology or conserved sequence motifs. Instead, they more closely resemble proteins in the alkaline ceramidase family and they may possess enzymatic activity. In the present paper, we highlight the evidence in support of each model and what is currently known for PAQR signal transduction of this non-canonical receptor.


2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Edgar Ricardo Vázquez-Martínez ◽  
Claudia Bello-Alvarez ◽  
Ana Lorena Hermenegildo-Molina ◽  
Mario Solís-Paredes ◽  
Sandra Parra-Hernández ◽  
...  

Endometriosis is one of the most frequent gynecological diseases in reproductive age women, but its etiology is not completely understood. Endometriosis is characterized by progesterone resistance, which has been explained in part by a decrease in the expression of the intracellular progesterone receptor in the ectopic endometrium. Progesterone action is also mediated by nongenomic mechanisms via membrane progesterone receptors (mPRs) that belong to the class II members of the progesterone and adipoQ receptor (PAQR) family. The aim of the present study was to evaluate the expression at mRNA and protein levels of mPR members in the eutopic and ectopic endometrium of women with endometriosis. Total RNA and total protein were isolated from control endometrium (17 samples), eutopic endometrium (17 samples), and ectopic endometrium (9 samples). The expression of PAQR7 (mPRα), PAQR8 (mPRβ), and PAQR6 (mPRδ) at mRNA and protein levels was evaluated by RT-qPCR and Western blot, whereas PAQR5 (mPRγ) gene expression was evaluated by RT-qPCR. Statistical analysis between comparable groups was performed using one-way ANOVA followed by Tukey’s multiple comparisons test with a confidence interval of 95 %. The analysis of gene expression showed that PAQR7 and PAQR5 expression was lower in both eutopic and ectopic endometrium as compared to the endometrium of women without endometriosis, whereas the expression of PAQR8 and PAQR6 was only reduced in eutopic endometrium. Furthermore, mPRα and mPRβ protein content was decreased in the ectopic endometrium of women with endometriosis. Our results demonstrate a decrease in the expression and protein content of mPRs in eutopic and ectopic endometrium of patients with endometriosis, which could contribute to the progesterone resistance observed in patients with this disease.


2020 ◽  
Author(s):  
EDGAR RICARDO VAZQUEZ-MARTINEZ ◽  
Claudia Bello-Álvarez ◽  
Ana Lorena Hermenegildo-Molina ◽  
Mario Solís-Paredes ◽  
Sandra Parra-Hernández ◽  
...  

Abstract Background: Endometriosis is one of the most frequent gynecological diseases in reproductive age women, but its etiology is not completely understood. Endometriosis is characterized by progesterone resistance, which has been explained in part by a decrease in the expression of the intracellular progesterone receptor in the ectopic endometrium. Progesterone action is also mediated by non-genomic mechanisms via membrane progesterone receptors that belong to the class II members of the progesterone and adipoQ receptor (PAQR) family. The aim of the present study was to evaluate the expression at mRNA and protein levels of PAQR family members in the eutopic and ectopic endometrium of women with endometriosis. Methods: Total RNA and total protein were isolated from control endometrium (17 samples), eutopic endometrium (17 samples), and ectopic endometrium (9 samples). The expression of PAQR7 ( mPRα ) , PAQR8 , (mPRβ) PAQR5 ( mPRγ ) , and PAQR6 ( mPRδ ) at mRNA and protein levels was evaluated by RT-qPCR and western blot. Statistical analysis between comparable groups was performed using one-way ANOVA followed by Tukey's multiple comparisons test with a confidence interval of 95%. Results: The analysis of gene expression showed that PAQR7 and PAQR5 expression was lower in both eutopic and ectopic endometrium as compared to the endometrium of women without endometriosis, whereas the expression of PAQR8 and PAQR6 was only reduced in eutopic endometrium. Furthermore, mPRα and mPRβ protein content was decreased in the ectopic endometrium of women with endometriosis. Conclusions: Our results demonstrate a decrease in the expression and protein content of mPRs in eutopic and ectopic endometrium of patients with endometriosis, which could contribute to the progesterone resistance observed in patients with this disease.


2020 ◽  
Author(s):  
EDGAR RICARDO VAZQUEZ-MARTINEZ ◽  
Claudia Bello-Alvarez ◽  
Ana Lorena Hermenegildo-Molina ◽  
Mario Solís-Paredes ◽  
Sandra Parra-Hernandez ◽  
...  

Abstract Background: Endometriosis is one of the most frequent gynecological diseases in reproductive age women, but its etiology is not completely understood. Endometriosis is characterized by progesterone resistance, which has been explained in part by a decrease in the expression of the intracellular progesterone receptor in the ectopic endometrium. Progesterone action is also mediated by non-genomic mechanisms via membrane progesterone receptors that belong to the class II members of the progesterone and adipoQ receptor (PAQR) family. The aim of the present study was to evaluate the expression at mRNA and protein levels of PAQR family members in the eutopic and ectopic endometrium of women with endometriosis. Methods : Total RNA and total protein were isolated from control endometrium (17 samples), eutopic endometrium (17 samples), and ectopic endometrium (9 samples). The expression of PAQR7 ( mPRα ) , PAQR8 , (mPRβ) PAQR5 ( mPRγ ) , and PAQR6 ( mPRδ ) at mRNA and protein levels was evaluated by RT-qPCR and western blot. Statistical analysis between comparable groups was performed using one-way ANOVA followed by Tukey's multiple comparisons test with a confidence interval of 95%. Results : The analysis of gene expression showed that PAQR7 and PAQR5 expression was lower in both eutopic and ectopic endometrium as compared to the endometrium of women without endometriosis, whereas the expression of PAQR8 and PAQR6 was only reduced in eutopic endometrium. Furthermore, mPRα and mPRβ protein content was decreased in the ectopic endometrium of women with endometriosis. Conclusions : Our results demonstrate a decrease in the expression and protein content of mPRs in eutopic and ectopic endometrium of patients with endometriosis, which could contribute to the progesterone resistance observed in patients with this disease.


Blood ◽  
1994 ◽  
Vol 84 (10) ◽  
pp. 3413-3421 ◽  
Author(s):  
A Szepesi ◽  
EW Gelfand ◽  
JJ Lucas

Abstract The proliferating cell nuclear antigen (PCNA) is an auxiliary protein of DNA polymerase delta and appears to be needed for both DNA synthesis and DNA repair. It is present in low amount in resting normal human T lymphocytes and, upon mitogenic stimulation with phorbol dibutyrate and ionomycin, begins to increase in mid-G1 phase, approximately 12 to 15 hours before entry into S phase. PCNA continues to increase in amount throughout the cell cycle and remains high in proliferating cultures. PCNA was extracted from activated normal T cells and from the transformed T-lymphoblastoid cell line Jurkat by a method that recovered approximately 98% of total cellular PCNA but yet retained its associations with other proteins. PCNA immunoprecipitates possessed H1 histone kinase activity, which increased in parallel with increasing cellular content of PCNA. Both the cdc2 and cdk2 kinases were found associated with PCNA in normal T cells, in amounts consistent with detected kinase activity. The results indicate that PCNA is not an inhibitory molecule of cdk/cyclin activity. Both normal and transformed T cells contained PCNA in association with cdk2, cdk4, cdk5, and cdk6, with the amount of PCNA associated with these molecules increasing in the order listed. Relatively high amounts of PCNA were also found associated with cyclins D2 and D3, the major cyclin partners of cdk6 in T cells. Though detected in normal cells, PCNA/cdc2 complexes were present in exceedingly low amount, if at all, in Jurkat cells. This cell line appeared to contain more of nearly all of the cdk and cyclin molecules analyzed, but there seemed to be little difference in the patterns of association of these molecules with PCNA in the cell line as compared with normal human T cells.


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