scholarly journals G-Protein Coupled Hormone Receptors of the Hypothalamic-Pituitary-Gonadal Axis are Targets of Endocrine Disrupting Chemicals

2021 ◽  
Author(s):  
Valentine Suteau ◽  
Patrice Rodien ◽  
Mathilde Munier
Keyword(s):  
G Protein ◽  
Hormone Receptors ◽  
Follicle Stimulating Hormone ◽  
Endocrine Disrupting Chemicals ◽  
Reproductive Function ◽  
Epidemiological Studies ◽  
Gonadotropin Releasing Hormone ◽  
Membrane Receptors ◽  
Endocrine Disrupting ◽  
G Protein Coupled

Endocrine-disrupting chemicals have received significant concern, since they ubiquitously persist in the environment and are able to induce adverse effects on health, and more particularly on reproductive function. Most of the studies focused on nuclear hormone receptors as mediators of sex steroid hormones signaling. However, there are increasing evidences that peptides hormones of the Hypothalamo-Pituitary-Gonadal axis are targets of endocrine-disrupting chemicals (as Gonadotropin-Releasing Hormone, Follicle-Stimulating Hormone, Luteinizing Hormone…). The majority of these hormones act on G protein-coupled membrane receptors. This review summarizes the effects of endocrine-disrupting chemicals on homeostasis of peptides hormone of Hypothalamo-Pituitary-Gonadal axis and on their G protein-coupled membrane receptors signaling revealed by experimental, clinical, and epidemiological studies in human.

scholarly journals Perturbation of Nuclear Hormone Receptors by Endocrine Disrupting Chemicals: Mechanisms and Pathological Consequences of Exposure

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 13 ◽  
Author(s):  
Julie M. Hall ◽  
Callie W. Greco
Keyword(s):  
Hormone Receptors ◽  
Endocrine Disrupting Chemicals ◽  
Type Ii Diabetes Mellitus ◽  
Epidemiological Studies ◽  
Nuclear Hormone Receptors ◽  
Sex Steroid Hormone ◽  
Organ Systems ◽  
Endocrine Disrupting ◽  
The Central Nervous System ◽  
And Function

Much of the early work on Nuclear Hormone Receptors (NHRs) focused on their essential roles as mediators of sex steroid hormone signaling in reproductive development and function, and thyroid hormone-dependent formation of the central nervous system. However, as NHRs display tissue-specific distributions and activities, it is not surprising that they are involved and vital in numerous aspects of human development and essential for homeostasis of all organ systems. Much attention has recently been focused on the role of NHRs in energy balance, metabolism, and lipid homeostasis. Dysregulation of NHR function has been implicated in numerous pathologies including cancers, metabolic obesity and syndrome, Type II diabetes mellitus, cardiovascular disease, hyperlipidemia, male and female infertility and other reproductive disorders. This review will discuss the dysregulation of NHR function by environmental endocrine disrupting chemicals (EDCs), and the associated pathological consequences of exposure in numerous tissues and organ systems, as revealed by experimental, clinical, and epidemiological studies.

scholarly journals Glycoprotein G-protein Coupled Receptors in Disease: Luteinizing Hormone Receptors and Follicle Stimulating Hormone Receptors

Diseases ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 35
Author(s):  
Duaa Althumairy ◽  
Xiaoping Zhang ◽  
Nicholas Baez ◽  
George Barisas ◽  
Deborah A. Roess ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
G Protein ◽  
Hormone Receptors ◽  
Follicle Stimulating Hormone ◽  
G Protein Coupled Receptors ◽  
Human Beings ◽  
Glycoprotein Hormone ◽  
Luteinizing Hormone Receptors ◽  
G Protein Coupled ◽  
Stimulating Hormone

Signal transduction by luteinizing hormone receptors (LHRs) and follicle-stimulating hormone receptors (FSHRs) is essential for the successful reproduction of human beings. Both receptors and the thyroid-stimulating hormone receptor are members of a subset of G-protein coupled receptors (GPCRs) described as the glycoprotein hormone receptors. Their ligands, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and a structurally related hormone produced in pregnancy, human chorionic gonadotropin (hCG), are large protein hormones that are extensively glycosylated. Although the primary physiologic functions of these receptors are in ovarian function and maintenance of pregnancy in human females and spermatogenesis in males, there are reports of LHRs or FSHRs involvement in disease processes both in the reproductive system and elsewhere. In this review, we evaluate the aggregation state of the structure of actively signaling LHRs or FSHRs, their functions in reproduction as well as summarizing disease processes related to receptor mutations affecting receptor function or expression in reproductive and non-reproductive tissues. We will also present novel strategies for either increasing or reducing the activity of LHRs signaling. Such approaches to modify signaling by glycoprotein receptors may prove advantageous in treating diseases relating to LHRs or FSHRs function in addition to furthering the identification of new strategies for modulating GPCR signaling.

Known and emerging factors modulating estrogenic effects of endocrine-disrupting chemicals

2014 ◽  
Vol 22 (1) ◽  
pp. 87-98 ◽  
Author(s):  
Wanglong Zhang ◽  
Yu Luo ◽  
Li Zhang ◽  
Qian Cai ◽  
Xuejun Pan
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
Posttranslational Modification ◽  
Splice Variants ◽  
Physiological Responses ◽  
Endocrine Disrupting Chemicals ◽  
Estrogenic Effects ◽  
Endocrine Disrupting ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

A variety of endocrine-disrupting chemicals (EDCs) have estrogenic effects and are termed xenoestrogens (XEs). The genomic pathway mediated by estrogen receptors (ERs) has been considered the major explanation for the estrogenic effects elicited by XEs. Presently, nongenomic pathways have achieved considerably more attention because the genomic pathways cannot fully elucidate many biological and physiological responses. Genomic and nongenomic pathways act either separately or cooperatively. XEs activate a variety of signaling pathways and downstream kinases, which in turn alter the posttranslational modification and activation of ERs. Classical ERs and their splice variants reside at the membrane and mediate rapid effects cooperatively with G protein-coupled estrogen receptor 1 (GPER), G protein, and many other signaling molecules. GPER seems more effective in mediating the synthetic chemical-induced effects. There are also feedback and feedforward mechanisms between both pathways. Numerous factors may affect both pathways. Recently, some new layers of regulation on the estrogenic effects were identified. In this review, we summarize these multiple regulation layers and discuss the newly identified factors.

scholarly journals Endocrine-Disrupting Chemicals: Some Actions of POPs on Female Reproduction

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Ewa L. Gregoraszczuk ◽  
Anna Ptak
Keyword(s):  
Hormone Receptors ◽  
Endocrine Disrupting Chemicals ◽  
Reproductive Function ◽  
Steroid Hormone Receptors ◽  
Female Reproduction ◽  
Aromatic Hydrocarbon Receptor ◽  
Activation Of Transcription ◽  
Endocrine Disrupting ◽  
The Impact ◽  
Ovarian Syndrome

Persistent organic pollutants (POPs), such as polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and polybrominated ethers (PBDEs), chloronaftalens (PCNs), and bisphenol A (BPA), are stable, lipophilic pollutants that affect fertility and cause serious reproductive problems, including ovotoxic action, lack of ovulation, premature ovarian failure (POF), or polycystic ovarian syndrome (PCOS). Most of the representatives of POPs influence the activation of transcription factors, not only activation of aromatic hydrocarbon receptor (AhR), but also the steroid hormone receptors. This minireview will focus on a variety of PAH activities in oocyte, ovary, placenta, and mammary gland. The complexity and diversity of factors belonging to POPs and disorders of the reproductive function of women indicate that the impact of environmental pollution as an important determinant factor in fertility should not be minimize.

scholarly journals Human Homologs of the Putative G Protein-Coupled Membrane Progestin Receptors (mPRα, β, and γ) Localize to the Endoplasmic Reticulum and Are Not Activated by Progesterone

2006 ◽  
Vol 20 (12) ◽  
pp. 3146-3164 ◽  
Author(s):  
Tom Krietsch ◽  
Maria Sofia Fernandes ◽  
Jukka Kero ◽  
Ralf Lösel ◽  
Maria Heyens ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
G Protein ◽  
Cell Lines ◽  
Spotted Seatrout ◽  
Membrane Receptors ◽  
Takifugu Rubripes ◽  
Camp Production ◽  
Intact Cells ◽  
Progestin Receptors ◽  
G Protein Coupled

Abstract The steroid hormone progesterone exerts pleiotrophic functions in many cell types. Although progesterone controls transcriptional activation through binding to its nuclear receptors, it also initiates rapid nongenomic signaling events. Recently, three putative membrane progestin receptors (mPRα, β, and γ) with structural similarity to G protein-coupled receptors have been identified. These mPR isoforms are expressed in a tissue-specific manner and belong to the larger, highly conserved family of progestin and adiponectin receptors found in plants, eubacteria, and eukaryotes. The fish mPRα has been reported to mediate progesterone-dependent MAPK activation and inhibition of cAMP production through coupling to an inhibitory G protein. To functionally characterize the human homologs, we established human embryonic kidney 293 and MDA-MB-231 cell lines that stably express human mPRα, β, or γ. For comparison, we also established cell lines expressing the mPRα cloned from the spotted seatrout (Cynoscion nebulosus) and Japanese pufferfish (Takifugu rubripes). Surprisingly, we found no evidence that human or fish mPRs regulate cAMP production or MAPK (ERK1/2 or p38) activation upon progesterone stimulation. Furthermore, the mPRs did not couple to a highly promiscuous G protein subunit, Gαq5i, in transfection studies or provoke Ca2+ mobilization in response to progesterone. Finally, we demonstrate that transfected mPRs, as well as endogenous human mPRα, localize to the endoplasmic reticulum, and that their expression does not lead to increased progestin binding either in membrane preparations or in intact cells. Our results therefore do not support the concept that mPRs are plasma membrane receptors involved in transducing nongenomic progesterone actions.

scholarly journals Imaging of persistent cAMP signaling by internalized G protein-coupled receptors

2010 ◽  
Vol 45 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Davide Calebiro ◽  
Viacheslav O Nikolaev ◽  
Martin J Lohse
Keyword(s):  
G Protein ◽  
Intracellular Signaling ◽  
Current Model ◽  
Living Cells ◽  
G Protein Coupled Receptors ◽  
Membrane Receptors ◽  
Optical Methods ◽  
Camp Signaling ◽  
Gpcr Signaling ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) are the largest family of plasma membrane receptors. They mediate the effects of several endogenous cues and serve as important pharmacological targets. Although many biochemical events involved in GPCR signaling have been characterized in great detail, little is known about their spatiotemporal dynamics in living cells. The recent advent of optical methods based on fluorescent resonance energy transfer allows, for the first time, to directly monitor GPCR signaling in living cells. Utilizing these methods, it has been recently possible to show that the receptors for two protein/peptide hormones, the TSH and the parathyroid hormone, continue signaling to cAMP after their internalization into endosomes. This type of intracellular signaling is persistent and apparently triggers specific cellular outcomes. Here, we review these recent data and explain the optical methods used for such studies. Based on these findings, we propose a revision of the current model of the GPCR–cAMP signaling pathway to accommodate receptor signaling at endosomes.

scholarly journals Characterization of Two Fly LGR (Leucine-Rich Repeat-Containing, G Protein-Coupled Receptor) Proteins Homologous to Vertebrate Glycoprotein Hormone Receptors: Constitutive Activation of Wild-Type Fly LGR1 But Not LGR2 in Transfected Mammalian Cells**This study was supported by NIH Grant HD-23273. The GenBank submission number for fly LGR2 is AF274591.

Endocrinology ◽  
2000 ◽  
Vol 141 (11) ◽  
pp. 4081-4090 ◽  
Author(s):  
Shinya Nishi ◽  
Sheau Yu Hsu ◽  
Karen Zell ◽  
Aaron J. W. Hsueh
Keyword(s):  
G Protein ◽  
Hormone Receptors ◽  
Coupling Mechanism ◽  
Leucine Rich Repeat ◽  
G Protein Coupled Receptor ◽  
Glycoprotein Hormone ◽  
Glycoprotein Hormone Receptors ◽  
Signaling Mechanisms ◽  
G Protein Coupled

Abstract The receptors for lutropin (LH), FSH, and TSH belong to the large G protein-coupled receptor (GPCR) superfamily and are unique in having a large N-terminal extracellular (ecto-) domain important for interactions with the large glycoprotein hormone ligands. Recent studies indicated the evolution of a large family of the leucine-rich repeat-containing, G protein-coupled receptors (LGRs) with at least seven members in mammals. Based on the sequences of mammalian glycoprotein hormone receptors, we have identified a new LGR in Drosophila melanogaster and named it as fly LGR2 to distinguish it from the previously reported fly LH/FSH/TSH receptor (renamed as fly LGR1). Genomic analysis indicated the presence of 10 exons in fly LGR2 as compared with 16 exons in fly LGR1. The deduced fly LGR2 complementary DNA (cDNA) showed 43 and 64% similarity to the fly LGR1 in the ectodomain and transmembrane region, respectively. Comparison of 12 LGRs from diverse species indicated that these proteins can be divided into three subfamilies and fly LGR1 and LGR2 belong to different subfamilies. Potential signaling mechanisms were tested in human 293T cells overexpressing the fly receptors. Of interest, fly LGR1, but not LGR2, showed constitutive activity as reflected by elevated basal cAMP production in transfected cells. The basal activity of fly LGR1 was further augmented following point mutations of key residues in the intracellular loop 3 or transmembrane VI, similar to those found in patients with familial male precocious puberty. The present study reports the cloning of fly LGR2 and indicates that the G protein-coupling mechanism is conserved in fly LGR1 as compared with the mammalian glycoprotein hormone receptors. The characterization of fly receptors with features similar to mammalian glycoprotein hormone receptors allows a better understanding of the evolution of this unique group of GPCRs and future elucidation of their ligand signaling mechanisms.

scholarly journals Trans-Activation of Mutant Follicle-Stimulating Hormone Receptors Selectively Generates Only One of Two Hormone Signals

2004 ◽  
Vol 18 (4) ◽  
pp. 968-978 ◽  
Author(s):  
Inhae Ji ◽  
ChangWoo Lee ◽  
MyoungKun Jeoung ◽  
YongBum Koo ◽  
Gail A. Sievert ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
G Protein ◽  
Hormone Receptors ◽  
Transmembrane Domain ◽  
Signal Generation ◽  
Lh Receptor ◽  
Glycosyl Phosphatidylinositol ◽  
Mutant Receptors ◽  
G Protein Coupled ◽  
Hormone Signals

Abstract Previously, we reported that a liganded LH receptor (LHR) is capable of activating itself (cis-activation) and other nonliganded LHRs to induce cAMP (trans-activation). Trans-activation of the LHR raises two crucial questions. Is trans-activation unique to LHR or common to other G protein-coupled receptors? Does trans-activation stimulate phospholipase Cβ as it does adenylyl cyclase? To address these questions, two types of novel FSH receptors (FSHRs) were constructed, one defective in hormone binding and the other defective in signal generation. The FSHR, a G protein-coupled receptor, comprises two major domains, the N-terminal extracellular exodomain that binds the hormone and the membrane-associated endodomain that generates the hormone signals. For signal defective receptors, the exodomain was attached to glycosyl phosphatidylinositol (ExoGPI) or the transmembrane domain of CD8 immune receptor (ExoCD). ExoGPI and ExoCD can trans-activate another nonliganded FSH. Surprisingly, the trans-activation generates a signal to activate either adenylyl cyclase or phospholipase Cβ, but not both. These results indicate that trans-activation in these mutant receptors is selective and limited in signal generation, thus providing new approaches to investigating the generation of different hormone signals and a novel means to selectively generate a particular hormone signal. Our data also suggest that the FSHR’s exodomain could not trans-activate LHR.

A generic microfluidic biosensor of G protein-coupled receptor activation – impedance measurements of reversible morphological changes of reverse transfected HEK293 cells on microelectrodes

RSC Advances ◽  
2015 ◽  
Vol 5 (65) ◽  
pp. 52563-52570 ◽  
Author(s):  
Saurabh K. Srivastava ◽  
Rajesh Ramaneti ◽  
Margriet Roelse ◽  
Hien Duy Tong ◽  
Elwin X. Vrouwe ◽  
...  
Keyword(s):  
G Protein ◽  
Morphological Changes ◽  
Receptor Activation ◽  
Membrane Receptors ◽  
Hek293 Cells ◽  
G Protein Coupled Receptor ◽  
Impedance Measurements ◽  
Transfected Cells ◽  
Microfluidic Biosensor ◽  
G Protein Coupled

Flowcell with micro-IDEs (250–500 μm) covered with both stable and reverse transfected cells overexpressing membrane receptors to demonstrate impedance responses to serial injections of analyte.

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