scholarly journals Role of Estrogen Receptors in Male Reproductive Physiology

2016 ◽  
Vol 3 (1) ◽  
pp. 40-45 ◽  
Author(s):  
Richard R Lee ◽  
Karen P Phillips
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
Intracellular Signaling ◽  
Male Fertility ◽  
Reproductive Tract ◽  
Male Reproduction ◽  
Receptor Subtypes ◽  
G Protein Coupled

Canonical estrogen receptors (ER α/β) have a genomic mechanism of action, functioning as nuclear transcription factors for estrogen-dependent genes. Estrogen receptors are well established within the male reproductive tract with estrogen playing an essential role for male fertility. The recent characterization of novel G-protein coupled estrogen receptor GPR30 (alternatively known as GPER1), depending on non-genomic intracellular signaling pathways to transduce estrogenic signals, requires a re-examination of the roles of estrogen receptors in male reproduction. Further, the affinity of environmental estrogens (xenoestrogens) for estrogen receptor subtypes may provide additional understanding of the reproductive effects of these chemicals on male fertility. Here we review the structure and functions of each estrogen receptor within the context of male reproduction, with special consideration of the reproductive implications of xenoestrogen exposure. 

scholarly journals Estrogen-Dependent and -Independent Estrogen Receptor-α Signaling Separately Regulate Male Fertility

Endocrinology ◽  
2009 ◽  
Vol 150 (6) ◽  
pp. 2898-2905 ◽  
Author(s):  
Kerstin W. Sinkevicius ◽  
Muriel Laine ◽  
Tamara L. Lotan ◽  
Karolina Woloszyn ◽  
John H. Richburg ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Male Fertility ◽  
Reproductive Tract ◽  
Cell Function ◽  
Critical Role ◽  
Estrogen Receptor Α ◽  
Male Reproductive Tract ◽  
Efferent Ductule

Estrogen receptor-α (ERα) plays a critical role in male reproductive tract development and fertility. To determine whether estrogen-dependent and -independent ERα mechanisms are involved in male fertility, we examined male estrogen nonresponsive ERα knock-in mice. These animals have a point mutation (G525L) in the ligand-binding domain of ERα that significantly reduces interaction with, and response to, endogenous estrogens but does not affect growth factor activation of ligand-independent ERα pathways. Surprisingly, we found that ligand-independent ERα signaling is essential for concentrating epididymal sperm via regulation of efferent ductule fluid reabsorption. In contrast, estrogen-dependent ERα signaling is required for germ cell viability, most likely through support of Sertoli cell function. By treating estrogen nonresponsive ERα knock-in (ENERKI) mice with the ERα selective synthetic agonist propyl pyrazole triol, which is able to bind and activate G525L ERα in vivo, we discovered male fertility required neonatal estrogen-mediated ERα signaling. Thus, our work indicates both estrogen-dependent and -independent pathways play separable roles in male murine reproductive tract development and that the role of ERα in human infertility should be examined more closely.

scholarly journals G Protein-Coupled Estrogen Receptor 1 (GPER) as a Novel Target for Schizophrenia Drug Treatment

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Danielle S Macêdo ◽  
Lia Lira Olivier Sanders ◽  
Raimunda das Candeias ◽  
Cyntia de Freitas Montenegro ◽  
David Freitas de Lucena ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
G Protein ◽  
Brain Inflammation ◽  
Antipsychotic Treatment ◽  
New Class ◽  
Estrogen Receptor Modulators ◽  
Novel Target ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

Abstract The observation that a person’s sex influences the onset age of schizophrenia, the course of the disease, and antipsychotic treatment response suggests a possible role for estrogen receptors in the pathophysiology of schizophrenia. Indeed, treatment with adjunctive estrogen or selective estrogen receptor modulators (SERMs) are known to reduce schizophrenia symptoms. While estrogen receptors (ER)α and ERβ have been studied, a third and more recently discovered estrogen receptor, the G protein-coupled estrogen receptor 1 (GPER), has been largely neglected. GPER is a membrane receptor that regulates non-genomic estrogen functions, such as the modulation of emotion and inflammatory response. This review discusses the possible role of GPER in brain impairments seen in schizophrenia and in its potential as a therapeutic target. We conducted a comprehensive literature search in the PubMed/MEDLINE database, using the following search terms: “Schizophrenia,” “Psychosis,” “GPER1 protein,” “Estrogen receptors,” “SERMS,” “GPER1 agonism, “Behavioral symptoms,” “Brain Inflammation.” Studies involving GPER in schizophrenia, whether preclinical or human studies, have been scarce, but the results are encouraging. Agonism of the GPER receptor could prove to be an essential mechanism of action for a new class of “anti-schizophrenia” drugs.

scholarly journals Kindlin-2 in Sertoli cells is essential for testis development and male fertility in mice

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Xiaochun Chi ◽  
Weiwei Luo ◽  
Jiagui Song ◽  
Bing Li ◽  
Tiantian Su ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Male Fertility ◽  
Nuclear Translocation ◽  
Hippo Pathway ◽  
Reproductive Organs ◽  
Male Reproduction ◽  
Barrier Structure ◽  
Male Mice ◽  
Sperm Development

AbstractKindlin-2 is known to play important roles in the development of mesoderm-derived tissues including myocardium, smooth muscle, cartilage and blood vessels. However, nothing is known for the role of Kindlin-2 in mesoderm-derived reproductive organs. Here, we report that loss of Kindlin-2 in Sertoli cells caused severe testis hypoplasia, abnormal germ cell development and complete infertility in male mice. Functionally, loss of Kindlin-2 inhibits proliferation, increases apoptosis, impairs phagocytosis in Sertoli cells and destroyed the integration of blood-testis barrier structure in testes. Mechanistically, Kindlin-2 interacts with LATS1 and YAP, the key components of Hippo pathway. Kindlin-2 impedes LATS1 interaction with YAP, and depletion of Kindlin-2 enhances LATS1 interaction with YAP, increases YAP phosphorylation and decreases its nuclear translocation. For clinical relevance, lower Kindlin-2 expression and decreased nucleus localization of YAP was found in SCOS patients. Collectively, we demonstrated that Kindlin-2 in Sertoli cells is essential for sperm development and male reproduction.

scholarly journals Decreased Expression of GPER1 Gene and Protein in Goiter

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Raquel Weber ◽  
Ana Paula Santin Bertoni ◽  
Laura Walter Bessestil ◽  
Ilma Simoni Brum ◽  
Tania Weber Furlanetto
Keyword(s):  
Estrogen Receptor ◽  
Quantitative Polymerase Chain Reaction ◽  
Thyroid Tissue ◽  
Chain Reaction ◽  
Normal Thyroid ◽  
Protein Levels ◽  
Protein Expressions ◽  
Polymerase Chain ◽  
G Protein Coupled

Goiter is more common in women, suggesting that estrogen could be involved in its physiopathology. The presence of classical estrogen receptors (ERαand ERβ) has been described in thyroid tissue, suggesting a direct effect of estrogen on the gland. A nonclassic estrogen receptor, the G-protein-coupled estrogen receptor (GPER1), has been described recently in several tissues. However, in goiter, the presence of this receptor has not been studied yet. We investigated GPER1 gene and protein expressions in normal thyroid and goiter using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively. In normal thyroid (n=16) and goiter (n=19), GPER1 gene was expressed in all samples, while GPER1 protein was expressed in all samples of normal thyroid (n=15) but in only 72% of goiter samples (n=13). When comparing GPER1 gene and protein levels in both conditions, gene expression and protein levels were higher in normal thyroid than in goiter, suggesting a role of this receptor in this condition. Further studies are needed to elucidate the role of GPER1 in normal thyroid and goiter.

Expression pattern of estrogen receptors α and β and G-protein-coupled estrogen receptor 1 in the human testis

2014 ◽  
Vol 142 (4) ◽  
pp. 421-432 ◽  
Author(s):  
Daniela Fietz ◽  
Clara Ratzenböck ◽  
Katja Hartmann ◽  
Oksana Raabe ◽  
Sabine Kliesch ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
G Protein ◽  
Expression Pattern ◽  
Human Testis ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

Postnatal Expression Patterns of Estrogen Receptor Subtypes and Choline Acetyltransferase in Different Regions of the Papez Circuit

2019 ◽  
Vol 41 (3-4) ◽  
pp. 203-211 ◽  
Author(s):  
Yu-xiang Wang ◽  
Lin Zhu ◽  
Li-xia Li ◽  
Hui-nan Xu ◽  
Hong-gang Wang ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Choline Acetyltransferase ◽  
Brain Area ◽  
Expression Patterns ◽  
Female Rats ◽  
Long Term Memory ◽  
Receptor Subtypes ◽  
Brain Functions ◽  
Papez Circuit ◽  
G Protein Coupled

The Papez circuit is crucial for several brain functions, including long-term memory and emotion. Estradiol modulates cognitive functions based on the expression pattern of its receptor subtypes including estrogen receptor (ER) α, β, and G protein-coupled receptor 30 (GPR30). Similarly, the activity in the cholinergic system correlates with several brain functions, such as learning and memory. In this study, we used immunofluorescence to examine the expression patterns of ERβ and Western blotting to analyze GPR30 and choline acetyltransferase (ChAT) expression, in different regions of the Papez circuit, including the prefrontal cortex, hippocampus, hypothalamus, anterior nucleus of the thalamus, and cingulum in female rats at postnatal days (PND) 1, 10, and 56. Our main finding was that the highest expression of ERβ and GPR30 was noted in each brain area of the Papez circuit in the PND1 rats, whereas the expression of ChAT was the highest in PND10 rats. These results provide vital information on the postnatal expression patterns of ER subtypes and ChAT in different regions of the Papez circuit.

scholarly journals Perspectives on the Role of Non-Coding RNAs in the Regulation of Expression and Function of the Estrogen Receptor

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2162
Author(s):  
Mohammad Taheri ◽  
Hamed Shoorei ◽  
Marcel E. Dinger ◽  
Soudeh Ghafouri-Fard
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
Reproductive System ◽  
Estrogen Regulation ◽  
Tissue Specific ◽  
Membrane Bound ◽  
Non Coding Rnas ◽  
And Function ◽  
G Protein Coupled

Estrogen receptors (ERs) comprise several nuclear and membrane-bound receptors with different tissue-specific functions. ERα and ERβ are two nuclear members of this family, whereas G protein-coupled estrogen receptor (GPER), ER-X, and Gq-coupled membrane estrogen receptor (Gq-mER) are membrane-bound G protein-coupled proteins. ERα participates in the development and function of several body organs such as the reproductive system, brain, heart and musculoskeletal systems. ERβ has a highly tissue-specific expression pattern, particularly in the female reproductive system, and exerts tumor-suppressive roles in some tissues. Recent studies have revealed functional links between both nuclear and membrane-bound ERs and non-coding RNAs. Several oncogenic lncRNAs and miRNAs have been shown to exert their effects through the modulation of the expression of ERs. Moreover, treatment with estradiol has been shown to alter the malignant behavior of cancer cells through functional axes composed of non-coding RNAs and ERs. The interaction between ERs and non-coding RNAs has functional relevance in several human pathologies associated with estrogen regulation, such as cancers, intervertebral disc degeneration, coronary heart disease and diabetes. In the current review, we summarize scientific literature on the role of miRNAs and lncRNAs on ER-associated signaling and related disorders.

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.

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