scholarly journals The role of G-protein-coupled membrane estrogen receptor in mouse Leydig cell function—in vivo and in vitro evaluation

2018 ◽  
Vol 374 (2) ◽  
pp. 389-412 ◽  
Author(s):  
M. Kotula-Balak ◽  
P. Pawlicki ◽  
A. Milon ◽  
W. Tworzydlo ◽  
M. Sekula ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
Leydig Cell ◽  
Cell Function ◽  
G Protein Coupled ◽  
Mouse Leydig Cell ◽  
Leydig Cell Function

scholarly journals The treatment effects of flaxseed-derived secoisolariciresinol diglycoside and its metabolite enterolactone on benign prostatic hyperplasia involve the G protein-coupled estrogen receptor 1

2016 ◽  
Vol 41 (12) ◽  
pp. 1303-1310 ◽  
Author(s):  
Guan-Yu Ren ◽  
Chun-Yang Chen ◽  
Wei-Guo Chen ◽  
Ya Huang ◽  
Li-Qiang Qin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Estrogen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
G Protein ◽  
Therapeutic Potential ◽  
Prostatic Hyperplasia ◽  
Docking Simulations ◽  
G Protein Coupled

Secoisolariciresinol diglucoside (SDG), a lignan extracted from flaxseed, has been shown to suppress benign prostatic hyperplasia (BPH). However, little is known about the mechanistic basis for its anti-BPH activity. The present study showed that enterolactone (ENL), the mammalian metabolite of SDG, shared the similar binding site of G1 on a new type of membranous estrogen receptor, G-protein-coupled estrogen eceptor 1 (GPER), by docking simulations method. ENL and G1 (the specific agonist of GPER) inhibited the proliferation of human prostate stromal cell line WPMY-1 as shown by MTT assay and arrested cell cycle at the G0/G1 phase, which was displayed by propidium iodide staining following flow cytometer examination. Silencing GPER by short interfering RNA attenuated the inhibitory effect of ENL on WPMY-1 cells. The therapeutic potential of SDG in the treatment of BPH was confirmed in a testosterone propionate-induced BPH rat model. SDG significantly reduced the enlargement of the rat prostate and the number of papillary projections of prostatic alveolus and thickness of the pseudostratified epithelial and stromal cells when comparing with the model group. Mechanistic studies showed that SDG and ENL increased the expression of GPER both in vitro and in vivo. Furthermore, ENL-induced cell cycle arrest may be mediated by the activation of GPER/ERK pathway and subsequent upregulation of p53 and p21 and downregulation of cyclin D1. This work, in tandem with previous studies, will enhance our knowledge regarding the mechanism(s) of dietary phytochemicals on BPH prevention and ultimately expand the scope of adopting alternative approaches in BPH treatment.

scholarly journals G Protein-Coupled Estrogen Receptor 1 Regulates Human Neutrophil Functions

2017 ◽  
Vol 2 (1) ◽  
pp. 1-13 ◽  
Author(s):  
M. Carmen Rodenas ◽  
Nicola Tamassia ◽  
Isabel Cabas ◽  
Federica Calzetti ◽  
José Meseguer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Protein Kinase ◽  
G Protein ◽  
Respiratory Burst ◽  
Human Neutrophils ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

Background: The role of estrogens in immune functioning is relatively well known under both physiological and pathological conditions. Neutrophils are the most abundant circulating leukocytes in humans, and their abundance and function are regulated by estrogens, since they express estrogen receptors (ERs). Traditionally, estrogens were thought to act via classical nuclear ERs, namely ERα and ERβ. However, it was observed that some estrogens induced biological effects only minutes after their application. This rapid, “nongenomic” effect of estrogens is mediated by a membrane-anchored receptor called G protein-coupled estrogen receptor 1 (GPER1). Nevertheless, the expression and role of GPER1 in the immune system has not been exhaustively studied, and its relevance in neutrophil functions remains unknown. Methods: Human neutrophils were incubated in vitro with 10-100 µM of the GPER1-specific agonist G1 alone or in combination with lipopolysaccharide. GPER1 expression and subcellular localization, respiratory burst, life span, gene expression profile, and cell signaling pathways involved were then analyzed in stimulated neutrophils. Results: Human neutrophils express a functional GPER1 which regulates their functions through cAMP/protein kinase A/cAMP response element-binding protein, p38 mitogen-activated protein kinase, and extracellular regulated MAPK signaling pathways. Thus, GPER1 activation in vitro increases the respiratory burst of neutrophils, extends their life span, and drastically alters their gene expression profile. Conclusions: Our results demonstrate that GPER1 activation promotes the polarization of human neutrophils towards a proinflammatory phenotype and point to GPER1 as a potential therapeutic target in immune diseases where neutrophils play a key role.

scholarly journals The P2Y6 Receptor Stimulates Bone Resorption by Osteoclasts

Endocrinology ◽  
2011 ◽  
Vol 152 (10) ◽  
pp. 3706-3716 ◽  
Author(s):  
Isabel R. Orriss ◽  
Ning Wang ◽  
Geoffrey Burnstock ◽  
Timothy R. Arnett ◽  
Alison Gartland ◽  
...  
Keyword(s):  
Cell Function ◽  
Bone Cell ◽  
Extracellular Nucleotides ◽  
P2y6 Receptor ◽  
Tomographic Analysis ◽  
G Protein Coupled ◽  
Resorptive Activity

Accumulating evidence indicates that extracellular nucleotides, signaling through P2 receptors, play a significant role in bone remodeling. Osteoclasts (the bone-resorbing cell) and osteoblasts (the bone-forming cell) display expression of the G protein-coupled P2Y6 receptor, but the role of this receptor in modulating cell function is unclear. Here, we demonstrate that extracellular UDP, acting via P2Y6 receptors, stimulates the formation of osteoclasts from precursor cells, while also enhancing the resorptive activity of mature osteoclasts. Furthermore, osteoclasts derived from P2Y6 receptor-deficient (P2Y6R−/−) animals displayed defective function in vitro. Using dual energy x-ray absorptiometry scanning and microcomputed tomographic analysis we showed that P2Y6R−/− mice have increased bone mineral content, cortical bone volume, and cortical thickness in the long bones and spine, whereas trabecular bone parameters were unaffected. Histomorphometric analysis showed the perimeter of the bone occupied by osteoclasts on the endocortical and trabecular surfaces was decreased in P2Y6R−/− mice. Taken together these results show the P2Y6 receptor may play an important role in the regulation of bone cell function in vivo.

Effects of Ammonium Perfluorooctanoate on Leydig-Cell Function: In Vitro, in Vivo, and ex Vivo Studies

1995 ◽  
Vol 134 (1) ◽  
pp. 18-25 ◽  
Author(s):  
L.B. Biegel ◽  
R.C.M. Liu ◽  
M.E. Hurtt ◽  
J.C. Cook
Keyword(s):  
Leydig Cell ◽  
Cell Function ◽  
Ex Vivo ◽  
Leydig Cell Function

Growth hormone-induced STAT5B regulates Star gene expression through a cooperation with cJUN in mouse MA-10 Leydig cells

Endocrinology ◽  
2021 ◽  
Author(s):  
Pierre-Olivier Hébert-Mercier ◽  
Francis Bergeron ◽  
Nicholas M Robert ◽  
Samir Mehanovic ◽  
Kenley Joule Pierre ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Cell Function ◽  
Mrna Levels ◽  
Leydig Cell Function ◽  
Star Gene

Abstract Leydig cells produce androgens that are essential for male sex differentiation and reproductive function. Leydig cell function is regulated by several hormones and signaling molecules, including growth hormone (GH). Although GH is known to upregulate Star gene expression in Leydig cells, its molecular mechanism of action remains unknown. The STAT5B transcription factor is a downstream effector of GH signaling in other systems. While STAT5B is present in both primary and Leydig cell lines, its function in these cells has yet to be ascertained. Here we report that treatment of MA-10 Leydig cells with GH or overexpression of STAT5B induces Star mRNA levels and increases steroid hormone output. The mouse Star promoter contains a consensus STAT5B element (TTCnnnGAA) at -756 bp to which STAT5B binds in vitro (EMSA and supershift) and in vivo (ChIP) in a GH-induced manner. In functional promoter assays, STAT5B was found to activate a -980 bp mouse Star reporter. Mutating the -756 bp element prevented STAT5B binding but did not abrogate STAT5B-responsiveness. STAT5B was found to functionally cooperate with DNA-bound cJUN. The STAT5B/cJUN cooperation was only observed in Leydig cells and not in Sertoli or fibroblast cells, indicating that additional Leydig cell-enriched transcription factors are required. The STAT5B/cJUN cooperation was lost only when both STAT5B and cJUN elements were mutated. In addition to identifying the Star gene as a novel target for STAT5B in Leydig cells, our data provide important new insights into the mechanism of GH and STAT5B action in the regulation of Leydig cell function.

scholarly journals Role of G protein-coupled receptor 1 in choriocarcinoma progression

2019 ◽  
Vol 317 (3) ◽  
pp. C556-C565 ◽  
Author(s):  
Binbin Huang ◽  
Wen Zhu ◽  
Junlei Chang ◽  
Xiaoyong Dai ◽  
Guiyuan Yu ◽  
...  
Keyword(s):  
G Protein ◽  
Drug Distribution ◽  
Chemotherapeutic Agents ◽  
G Protein Coupled Receptor ◽  
Amino Acid Peptide ◽  
Erk Phosphorylation ◽  
G Protein Coupled

Choriocarcinoma is characterized by malignant proliferation and transformation of trophoblasts and is currently treated with systemic chemotherapeutic agents. The lack of specific targets for chemotherapeutic agents results in indiscriminate drug distribution. In our study, we aimed to delineate the mechanism by which G protein-coupled receptor 1 (GPR1) regulates the development of choriocarcinoma and thus investigated GPR1 as a prospective chemotherapeutic target. In this study, GPR1 expression levels were examined in several trophoblast cell lines. We found significantly higher GPR1 expression in choriocarcinoma cells (JEG3 and BeWo) than in normal trophoblast cells (HTR-8/SVneo). Additionally, we studied the role of GPR1 in choriocarcinoma in vitro and in vivo. GPR1 knockdown suppressed proliferation, invasion, and Akt and ERK phosphorylation in vitro and slowed tumor growth in vivo. Interestingly, GPR1 overexpression promoted increased proliferation, invasion, and Akt and ERK phosphorylation in vitro. Furthermore, we identified a specific GPR1-binding seven-amino acid peptide, LRH7-G3, that might also suppress choriocarcinoma in vitro and in vivo through phage display. Our study is the first to report that GPR1 may play a role in regulating choriocarcinoma progression through the Akt and ERK pathways. GPR1 could be a promising potential pharmaceutical target for choriocarcinoma.

Environmental toxins

2013 ◽  
Vol 33 (10) ◽  
pp. 1017-1039 ◽  
Author(s):  
Pallav Sengupta ◽  
Rajdeb Banerjee
Keyword(s):  
Literature Review ◽  
Leydig Cell ◽  
Cell Function ◽  
Pesticide Exposure ◽  
Semen Quality ◽  
Reproductive Physiology ◽  
Environmental Toxins ◽  
Leydig Cell Function

This review comprehensively summarizes the effects of more than 15 mostly used pesticides on male reproductive physiology, as recent experimental and epidemiological research have indicated their alarming impact on overall human health. Mechanisms have described that pesticide exposure damages spermatozoa, alter Sertoli or Leydig cell function, both in vitro and in vivo and thus affects semen quality. But, the literature suggests a need for more intricate research in those pesticides that are defined as mutagens or carcinogens and directly affect the hypothalamic–pituitary–gonadal axis. This literature review also proposes specific solutions to overcome these health effects.

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