Abstract:Estrogen toxicity has been an area of priority in aquatic toxicology over the last 20 yr. Currently, estrogen toxicity is primarily linked to classical estrogen signaling, the interaction of estrogen receptors alpha and beta (ERα and ERβ). Recent evidence has indicated that a rapid, nongenomic, nonclassical estrogen signaling pathway exists via the G protein–coupled estrogen receptor (GPER), which is expressed in many biological systems, with roles in the cardiovascular system. The objective of the present stu… Show more
“…However, the convergence with the effect of xenoestrogens on the heart rate is indicated by Anderson et al [ 48 ] where the significant bradycardic effect of EE2 (0.1, 1, 10, 100, and 1000 ng/L) was observed on the heart rate of the medaka embryos. In addition, using selected estrogen receptor modulators (ERMs) it has been shown that estrogen-induced bradycardia appears to be associated with GPER and not with ERα and ERβ.…”
Section: Impact On Circulatory Systemmentioning
confidence: 97%
“…The literature was searched between 1 October 2021 and 17 February 2022 in the Google Scholar, Web of Science and Scopus databases using the following entries: estrogen receptors, diseases, fish, Danio, Medaka, Oryzias, cardiovascular, immunology, cancer, metabolism, estrogens, xenoestrogens, reproduction, Common carp, Sea Bass, Grass Carp, Atlantic salmon, Rainbow trout, Sea bream, Nile tilapia, teleost fish. Figure 1 Presence of selected receptors in tissues of teleost fishes and potential disruptions of related pathways [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. …”
Section: Introductionmentioning
confidence: 99%
“… Presence of selected receptors in tissues of teleost fishes and potential disruptions of related pathways [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. …”
Estrogen receptors (ERs) play a key role in many biochemical and physiological processes, that are involved in maintaining organism homeostasis. At the most basic level, they can be divided into nuclear estrogen receptors and membrane estrogen receptors that imply their effect in two ways: slower genomic, and faster non-genomic. In these ways, estrogens and xenoestrogens can negatively affect animal health and welfare. Most of the available literature focuses on human and mammalian physiology, and clearly, we can observe a need for further research focusing on complex mutual interactions between different estrogens and xenoestrogens in aquatic animals, primarily fishes. Understanding the mechanisms of action of estrogenic compounds on the ERs in fishes and their negative consequences, may improve efforts in environmental protection of these animals and their environment and benefit society in return. In this review, we have summarized the ER-mediated effects of xenoestrogens and estrogens on teleost fishes metabolism, their carcinogenic potential, immune, circulatory, and reproductive systems.
“…However, the convergence with the effect of xenoestrogens on the heart rate is indicated by Anderson et al [ 48 ] where the significant bradycardic effect of EE2 (0.1, 1, 10, 100, and 1000 ng/L) was observed on the heart rate of the medaka embryos. In addition, using selected estrogen receptor modulators (ERMs) it has been shown that estrogen-induced bradycardia appears to be associated with GPER and not with ERα and ERβ.…”
Section: Impact On Circulatory Systemmentioning
confidence: 97%
“…The literature was searched between 1 October 2021 and 17 February 2022 in the Google Scholar, Web of Science and Scopus databases using the following entries: estrogen receptors, diseases, fish, Danio, Medaka, Oryzias, cardiovascular, immunology, cancer, metabolism, estrogens, xenoestrogens, reproduction, Common carp, Sea Bass, Grass Carp, Atlantic salmon, Rainbow trout, Sea bream, Nile tilapia, teleost fish. Figure 1 Presence of selected receptors in tissues of teleost fishes and potential disruptions of related pathways [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. …”
Section: Introductionmentioning
confidence: 99%
“… Presence of selected receptors in tissues of teleost fishes and potential disruptions of related pathways [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. …”
Estrogen receptors (ERs) play a key role in many biochemical and physiological processes, that are involved in maintaining organism homeostasis. At the most basic level, they can be divided into nuclear estrogen receptors and membrane estrogen receptors that imply their effect in two ways: slower genomic, and faster non-genomic. In these ways, estrogens and xenoestrogens can negatively affect animal health and welfare. Most of the available literature focuses on human and mammalian physiology, and clearly, we can observe a need for further research focusing on complex mutual interactions between different estrogens and xenoestrogens in aquatic animals, primarily fishes. Understanding the mechanisms of action of estrogenic compounds on the ERs in fishes and their negative consequences, may improve efforts in environmental protection of these animals and their environment and benefit society in return. In this review, we have summarized the ER-mediated effects of xenoestrogens and estrogens on teleost fishes metabolism, their carcinogenic potential, immune, circulatory, and reproductive systems.
“…It is GPER1, while not ERα and ERβ, plays an important role in estrogenresponded heart rate regulation [45,46]. GPER1 activation has a cardioprotective effect on heart failure in male mice and myocardial inflammation in male spontaneously hypertensive rats (SHRs), adriamycin-induced cardiotoxicity in male rats can be alleviated by GPER1 activation, and myocardial cell death can also be protected by GPER1 activation [47][48][49][50].…”
Section: Gper Roles In Cardiovascular Systemmentioning
Estrogen binds to the typical estrogen receptor (ER) ERα or ERβ and is translocated to the nucleus, where it binds directly to the estrogen response element of the target gene to induce transcription and regulate gene expression, and the whole process is completed in several hours to several days. The G protein-coupled estrogen receptor (GPER), a type that is structurally distinct from typical ERα and ERβ, rapidly induces most non-genomic effects within seconds to minutes. GPER regulates cell growth, migration, and programmed cell death in a variety of tissues and has been associated with the progression of estrogen-associated cancers. Here, the characteristics, cell signal transduction, and the latest research progress of GPER in estrogen-associated tumors and retinal diseases are reviewed.
“…Estrogen-induced regulation of heart rate appears to be linked to GPER1 rather than ERα and Erβ [234,235]. In addition, GPER1 has been shown to modulate maternal estrogen levels in zebrafish, which are essential for appropriate embryonic heart rates [235].…”
Cardiovascular (CV) and renal diseases are increasingly prevalent in the United States and globally. CV-related mortality is the leading cause of death in the United States, while renal-related mortality is the 8th. Despite advanced therapeutics, both diseases persist, warranting continued exploration of disease mechanisms to develop novel therapeutics and advance clinical outcomes for cardio-renal health. CV and renal diseases increase with age, and there are sex differences evident in both the prevalence and progression of CV and renal disease. These age and sex differences seen in cardio-renal health implicate sex hormones as potentially important regulators to be studied. One such regulator is G protein-coupled estrogen receptor 1 (GPER1). GPER1 has been implicated in estrogen signaling and is expressed in a variety of tissues including the heart, vasculature, and kidney. GPER1 has been shown to be protective against CV and renal diseases in different experimental animal models. GPER1 actions involve multiple signaling pathways: interaction with aldosterone and endothelin-1 signaling, stimulation of the release of nitric oxide, and reduction in oxidative stress, inflammation, and immune infiltration. This review will discuss the current literature regarding GPER1 and cardio-renal health, particularly in the context of aging. Improving our understanding of GPER1-evoked mechanisms may reveal novel therapeutics aimed at improving cardio-renal health and clinical outcomes in the elderly.
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