Background: Gonadotropins are glycoprotein hormones fundamental in the endocrine regulation of reproduction. They act on structurally similar members of G protein-coupled receptors (GPCRs) expressed exclusively in the gonads and support gametogenesis, sex steroid synthesis, and pregnancy. While it is a common opinion that the gonadotropin receptors act as a single molecule entity (monomer), increasing evidence underlines the formation of molecular complexes involving multiple receptors.
Objectives: To review current knowledge of membrane receptor-receptor interactions in reproduction.
Results And Discussion: Homo/heteromers of gonadotropin receptors may act as allosteric modulators, act as biased agonist and/or cooperate in sustaining intracellular signals fundamental to support reproduction. Technical limitations lead to in vitro data that require to be confirmed in vivo to figure out the physiological impact of gonadotropin receptor assemblies.
Conclusions: Gonadotropin receptor homo/heteromers provide a new field of research that deserves attention for possible clinical and therapeutic implications in physiology and pathophysiology.
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http://dx.doi.org/10.1111/andr.13821 | DOI Listing |
Andrology
December 2024
Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Background: Gonadotropins are glycoprotein hormones fundamental in the endocrine regulation of reproduction. They act on structurally similar members of G protein-coupled receptors (GPCRs) expressed exclusively in the gonads and support gametogenesis, sex steroid synthesis, and pregnancy. While it is a common opinion that the gonadotropin receptors act as a single molecule entity (monomer), increasing evidence underlines the formation of molecular complexes involving multiple receptors.
View Article and Find Full Text PDFBiochim Biophys Acta Biomembr
January 2025
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore; Department of Biology, Syracuse University, NY 13244, USA; Interdisciplinary Neuroscience Program, Syracuse University, NY 13244, USA. Electronic address:
Tumor necrosis factor receptors (TNFR1 and TNFR2) play key roles in mediating inflammatory response and cell death signaling, which are associated with autoimmune disorders, neurodegenerative diseases, and cancers. The structure-function relationships of TNF receptors and their ligands determine the activation or inhibition of downstream signaling pathways. Available crystal structures have provided critical insights into the therapeutic targeting strategies of TNF receptors and their signaling networks.
View Article and Find Full Text PDFInt J Mol Sci
August 2024
Department of Earth, Environment and Life Sciences, University of Genova, Viale Benedetto XV 5, 16132 Genova, Italy.
The receptor-receptor interaction (RRI) of G protein-coupled receptors (GPCRs) leads to new functional entities that are conceptually distinct from the simple addition of signals mediated by the activation of the receptors that form the heteromers. Focusing on astrocytes, there is evidence for the existence of inhibitory and facilitatory RRIs, including the heteromers formed by the adenosine A2A and the dopamine D2 receptors, by A2A and the oxytocin receptor (OTR), and the D2-OTR heteromers. The possible involvement of these receptors in mosaicism has never been investigated in striatal astrocytes.
View Article and Find Full Text PDFFront Physiol
July 2024
Section of Human Anatomy, Department of Neuroscience, University of Padova, Padua, Italy.
Dopamine and histamine receptors DR and HR are G protein-coupled receptors (GPCRs) which can establish physical receptor-receptor interactions (RRIs), leading to homo/hetero-complexes in a dynamic equilibrium. Although DR and HR expression has been detected within the carotid body (CB), their possible heterodimerization has never been demonstrated. The aim of this work was to verify DR and HR colocalization in the CB, thus suggesting a possible interplay that, in turn, may be responsible of specific DR-HR antagonistic functional implications.
View Article and Find Full Text PDFRes Sq
July 2024
Department of Physics, University of Wisconsin-Milwaukee, WI 53211, USA.
The functional significance of the interactions between proteins in living cells to form short-lived quaternary structures cannot be overemphasized. Yet, quaternary structure information is not captured by current methods, neither can those methods determine structure within living cells. The dynamic versatility, abundance, and functional diversity of G protein-coupled receptors (GPCRs) pose myriad challenges to existing technologies but also present these proteins as the ideal testbed for new technologies to investigate the complex inter-regulation of receptor-ligand, receptor-receptor, and receptor-downstream effector interfaces in living cells.
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