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Julie Gonin - One of the best experts on this subject based on the ideXlab platform.
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Expression of Follicle-Stimulating Hormone Receptor by the vascular endothelium in tumor metastases
BMC Cancer, 2013Co-Authors: Ahsan Siraj, François Planeix, Christophe Pichon, Virginie Desestret, Martine Antoine, Gaëlle Fromont, Michel Huerre, Marc Sanson, Philippe Camparo, Julie GoninAbstract:Background The Follicle Stimulating Hormone Receptor (FSHR) is expressed by the vascular endothelium in a wide range of human tumors. It was not determined however if FSHR is present in metastases which are responsible for the terminal illness.
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Expression of Follicle-Stimulating Hormone Receptor by the vascular endothelium in tumor metastases.
BMC Cancer, 2013Co-Authors: Ahsan Siraj, François Planeix, Christophe Pichon, Virginie Desestret, Martine Antoine, Gaëlle Fromont, Michel Huerre, Marc Sanson, Philippe Camparo, Julie GoninAbstract:BACKGROUND: The Follicle Stimulating Hormone Receptor (FSHR) is expressed by the vascular endothelium in a wide range of human tumors. It was not determined however if FSHR is present in metastases which are responsible for the terminal illness. METHODS: We used immunohistochemistry based on a highly FSHR-specific monoclonal antibody to detect FSHR in cancer metastases from 6 major tumor types (lung, breast, prostate, colon, kidney, and leiomyosarcoma ) to 6 frequent locations (bone, liver, lymph node, brain, lung, and pleura) of 209 patients. RESULTS: In 166 patients examined (79%), FSHR was expressed by blood vessels associated with metastatic tissue. FSHR-positive vessels were present in the interior of the tumors and some few millimeters outside, in the normally appearing tissue. In the interior of the metastases, the density of the FSHR-positive vessels was constant up to 7 mm, the maximum depth available in the analyzed sections. No significant differences were noticed between the density of FSHR-positive vessels inside vs. outside tumors for metastases from lung, breast, colon, and kidney cancers. In contrast, for prostate cancer metastases, the density of FSHR-positive vessels was about 3-fold higher at the exterior of the tumor compared to the interior. Among brain metastases, the density of FSHR-positive vessels was highest in lung and kidney cancer, and lowest in prostate and colon cancer. In metastases of breast cancer to the lung pleura, the percentage of blood vessels expressing FSHR was positively correlated with the progesterone Receptor level, but not with either HER-2 or estrogen Receptors. In normal tissues corresponding to the host organs for the analyzed metastases, obtained from patients not known to have cancer, FSHR staining was absent, with the exception of approx. 1% of the vessels in non tumoral temporal lobe epilepsy samples. CONCLUSION: FSHR is expressed by the endothelium of blood vessels in the majority of metastatic tumors.
Christophe Pichon - One of the best experts on this subject based on the ideXlab platform.
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Whole-cell biopanning with a synthetic phage display library of nanobodies enabled the recovery of Follicle-Stimulating Hormone Receptor inhibitors
Biochemical and Biophysical Research Communications, 2017Co-Authors: Ronan Crepin, François Planeix, Selma Djender, Anne Beugnet, Sandrine Moutel, Franck Perez, Christophe Pichon, Gianluca Veggiani, Sebastian Amigorena, Nicolae GhineaAbstract:Antibodies are essential reagents that are increasingly used in diagnostics and therapy. Their specificity and capacity to recognize their native antigen are critical characteristics for their in vivo application. Follicle-Stimulating Hormone Receptor is a GPCR protein regulating ovarian follicular maturation and spermatogenesis. Recently, its potentiality as a cancer biomarker has been demonstrated but no antibody suitable for in vivo tumor targeting and treatment has been characterized so far. In this paper we describe the first successful attempt to recover recombinant antibodies against the FSHR and that: i) are directly panned from a pre-immune library using whole cells expressing the target Receptor at their surface; ii) show inhibitory activity towards the FSH-induced cAMP accumulation; iii) do not share the same epitope with the natural binder FSH; iv) can be produced inexpensively as mono- or bivalent functional molecules in the bacterial cytoplasm. We expect that the proposed biopanning strategy will be profitable to identify useful functional antibodies for further members of the GPCR class.
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Follicle-Stimulating Hormone Receptor Expression in Endometriotic Lesions and the Associated Vasculature: An Immunohistochemical Study.
Reproductive Sciences, 2015Co-Authors: Blaise Robin, François Planeix, Christophe Pichon, Xavier Sastre-garau, Tine Kold Olesen, Jean Gogusev, Nicolae GhineaAbstract:Follicle-Stimulating Hormone Receptor (FSHR) is present on endothelial cells of blood vessels and endometrial glands of the proliferative and secretory endometrium. So far, the expression of FSHR in endometriosis has not been studied. We evaluated FSHR expression in 194 tissue specimens representing 3 relevant types of endometriosis: rectovaginal endometriotic nodules, ovarian endometriotic cysts, and peritoneal endometriotic implants. Specimens of normal endometrium were used as controls. Archival formalin-fixed and paraffin-embedded material was analyzed immunohistochemically with a highly specific monoclonal antihuman FSHR antibody using the peroxidase method. A robust vascular FSHR expression was found in all 194 patients, irrespective of the endometriosis lesion location. Follicle-Stimulating Hormone Receptor was not detected in normal host tissues located more than 5 mm from the lesions. The endometriotic lymphatic vessels do not express FSHR. The density of FSHR-positive vessels in patients with re...
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Endothelial Follicle-Stimulating Hormone Receptor expression in invasive breast cancer and vascular remodeling at tumor periphery.
Journal of Experimental & Clinical Cancer Research, 2015Co-Authors: François Planeix, Christophe Pichon, Martine Antoine, Blaise Robin, Xavier Sastre-garau, Mohammad-ahsan Siraj, François-clément Bidard, Nicolae GhineaAbstract:Background Follicle-Stimulating Hormone Receptor (FSHR) is expressed on the endothelial surface of blood vessels associated with solid tumor periphery, where angiogenesis is known to occur. The correlation between FSHR expression and formation of new peritumoral vessels has not been previously investigated.
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Expression of Follicle-Stimulating Hormone Receptor by the vascular endothelium in tumor metastases
BMC Cancer, 2013Co-Authors: Ahsan Siraj, François Planeix, Christophe Pichon, Virginie Desestret, Martine Antoine, Gaëlle Fromont, Michel Huerre, Marc Sanson, Philippe Camparo, Julie GoninAbstract:Background The Follicle Stimulating Hormone Receptor (FSHR) is expressed by the vascular endothelium in a wide range of human tumors. It was not determined however if FSHR is present in metastases which are responsible for the terminal illness.
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Expression of Follicle-Stimulating Hormone Receptor by the vascular endothelium in tumor metastases.
BMC Cancer, 2013Co-Authors: Ahsan Siraj, François Planeix, Christophe Pichon, Virginie Desestret, Martine Antoine, Gaëlle Fromont, Michel Huerre, Marc Sanson, Philippe Camparo, Julie GoninAbstract:BACKGROUND: The Follicle Stimulating Hormone Receptor (FSHR) is expressed by the vascular endothelium in a wide range of human tumors. It was not determined however if FSHR is present in metastases which are responsible for the terminal illness. METHODS: We used immunohistochemistry based on a highly FSHR-specific monoclonal antibody to detect FSHR in cancer metastases from 6 major tumor types (lung, breast, prostate, colon, kidney, and leiomyosarcoma ) to 6 frequent locations (bone, liver, lymph node, brain, lung, and pleura) of 209 patients. RESULTS: In 166 patients examined (79%), FSHR was expressed by blood vessels associated with metastatic tissue. FSHR-positive vessels were present in the interior of the tumors and some few millimeters outside, in the normally appearing tissue. In the interior of the metastases, the density of the FSHR-positive vessels was constant up to 7 mm, the maximum depth available in the analyzed sections. No significant differences were noticed between the density of FSHR-positive vessels inside vs. outside tumors for metastases from lung, breast, colon, and kidney cancers. In contrast, for prostate cancer metastases, the density of FSHR-positive vessels was about 3-fold higher at the exterior of the tumor compared to the interior. Among brain metastases, the density of FSHR-positive vessels was highest in lung and kidney cancer, and lowest in prostate and colon cancer. In metastases of breast cancer to the lung pleura, the percentage of blood vessels expressing FSHR was positively correlated with the progesterone Receptor level, but not with either HER-2 or estrogen Receptors. In normal tissues corresponding to the host organs for the analyzed metastases, obtained from patients not known to have cancer, FSHR staining was absent, with the exception of approx. 1% of the vessels in non tumoral temporal lobe epilepsy samples. CONCLUSION: FSHR is expressed by the endothelium of blood vessels in the majority of metastatic tumors.
François Planeix - One of the best experts on this subject based on the ideXlab platform.
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Whole-cell biopanning with a synthetic phage display library of nanobodies enabled the recovery of Follicle-Stimulating Hormone Receptor inhibitors
Biochemical and Biophysical Research Communications, 2017Co-Authors: Ronan Crepin, François Planeix, Selma Djender, Anne Beugnet, Sandrine Moutel, Franck Perez, Christophe Pichon, Gianluca Veggiani, Sebastian Amigorena, Nicolae GhineaAbstract:Antibodies are essential reagents that are increasingly used in diagnostics and therapy. Their specificity and capacity to recognize their native antigen are critical characteristics for their in vivo application. Follicle-Stimulating Hormone Receptor is a GPCR protein regulating ovarian follicular maturation and spermatogenesis. Recently, its potentiality as a cancer biomarker has been demonstrated but no antibody suitable for in vivo tumor targeting and treatment has been characterized so far. In this paper we describe the first successful attempt to recover recombinant antibodies against the FSHR and that: i) are directly panned from a pre-immune library using whole cells expressing the target Receptor at their surface; ii) show inhibitory activity towards the FSH-induced cAMP accumulation; iii) do not share the same epitope with the natural binder FSH; iv) can be produced inexpensively as mono- or bivalent functional molecules in the bacterial cytoplasm. We expect that the proposed biopanning strategy will be profitable to identify useful functional antibodies for further members of the GPCR class.
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Follicle-Stimulating Hormone Receptor Expression in Endometriotic Lesions and the Associated Vasculature: An Immunohistochemical Study.
Reproductive Sciences, 2015Co-Authors: Blaise Robin, François Planeix, Christophe Pichon, Xavier Sastre-garau, Tine Kold Olesen, Jean Gogusev, Nicolae GhineaAbstract:Follicle-Stimulating Hormone Receptor (FSHR) is present on endothelial cells of blood vessels and endometrial glands of the proliferative and secretory endometrium. So far, the expression of FSHR in endometriosis has not been studied. We evaluated FSHR expression in 194 tissue specimens representing 3 relevant types of endometriosis: rectovaginal endometriotic nodules, ovarian endometriotic cysts, and peritoneal endometriotic implants. Specimens of normal endometrium were used as controls. Archival formalin-fixed and paraffin-embedded material was analyzed immunohistochemically with a highly specific monoclonal antihuman FSHR antibody using the peroxidase method. A robust vascular FSHR expression was found in all 194 patients, irrespective of the endometriosis lesion location. Follicle-Stimulating Hormone Receptor was not detected in normal host tissues located more than 5 mm from the lesions. The endometriotic lymphatic vessels do not express FSHR. The density of FSHR-positive vessels in patients with re...
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Endothelial Follicle-Stimulating Hormone Receptor expression in invasive breast cancer and vascular remodeling at tumor periphery.
Journal of Experimental & Clinical Cancer Research, 2015Co-Authors: François Planeix, Christophe Pichon, Martine Antoine, Blaise Robin, Xavier Sastre-garau, Mohammad-ahsan Siraj, François-clément Bidard, Nicolae GhineaAbstract:Background Follicle-Stimulating Hormone Receptor (FSHR) is expressed on the endothelial surface of blood vessels associated with solid tumor periphery, where angiogenesis is known to occur. The correlation between FSHR expression and formation of new peritumoral vessels has not been previously investigated.
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Expression of Follicle-Stimulating Hormone Receptor by the vascular endothelium in tumor metastases
BMC Cancer, 2013Co-Authors: Ahsan Siraj, François Planeix, Christophe Pichon, Virginie Desestret, Martine Antoine, Gaëlle Fromont, Michel Huerre, Marc Sanson, Philippe Camparo, Julie GoninAbstract:Background The Follicle Stimulating Hormone Receptor (FSHR) is expressed by the vascular endothelium in a wide range of human tumors. It was not determined however if FSHR is present in metastases which are responsible for the terminal illness.
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Expression of Follicle-Stimulating Hormone Receptor by the vascular endothelium in tumor metastases.
BMC Cancer, 2013Co-Authors: Ahsan Siraj, François Planeix, Christophe Pichon, Virginie Desestret, Martine Antoine, Gaëlle Fromont, Michel Huerre, Marc Sanson, Philippe Camparo, Julie GoninAbstract:BACKGROUND: The Follicle Stimulating Hormone Receptor (FSHR) is expressed by the vascular endothelium in a wide range of human tumors. It was not determined however if FSHR is present in metastases which are responsible for the terminal illness. METHODS: We used immunohistochemistry based on a highly FSHR-specific monoclonal antibody to detect FSHR in cancer metastases from 6 major tumor types (lung, breast, prostate, colon, kidney, and leiomyosarcoma ) to 6 frequent locations (bone, liver, lymph node, brain, lung, and pleura) of 209 patients. RESULTS: In 166 patients examined (79%), FSHR was expressed by blood vessels associated with metastatic tissue. FSHR-positive vessels were present in the interior of the tumors and some few millimeters outside, in the normally appearing tissue. In the interior of the metastases, the density of the FSHR-positive vessels was constant up to 7 mm, the maximum depth available in the analyzed sections. No significant differences were noticed between the density of FSHR-positive vessels inside vs. outside tumors for metastases from lung, breast, colon, and kidney cancers. In contrast, for prostate cancer metastases, the density of FSHR-positive vessels was about 3-fold higher at the exterior of the tumor compared to the interior. Among brain metastases, the density of FSHR-positive vessels was highest in lung and kidney cancer, and lowest in prostate and colon cancer. In metastases of breast cancer to the lung pleura, the percentage of blood vessels expressing FSHR was positively correlated with the progesterone Receptor level, but not with either HER-2 or estrogen Receptors. In normal tissues corresponding to the host organs for the analyzed metastases, obtained from patients not known to have cancer, FSHR staining was absent, with the exception of approx. 1% of the vessels in non tumoral temporal lobe epilepsy samples. CONCLUSION: FSHR is expressed by the endothelium of blood vessels in the majority of metastatic tumors.
James A Dias - One of the best experts on this subject based on the ideXlab platform.
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Structure-Function Relationships of the Follicle-Stimulating Hormone Receptor
Frontiers in Endocrinology, 2018Co-Authors: Alfredo Ulloa-aguirre, Teresa Zariñán, Eduardo Jardón-valadez, Rubén Gutiérrez-sagal, James A DiasAbstract:The Follicle-Stimulating Hormone Receptor (FSHR) plays a crucial role in reproduction. This structurally complex Receptor belongs to the G-protein coupled Receptor (GPCR) superfamily of membrane Receptors. As with the other structurally similar glycoprotein Hormone Receptors (the thyroid-stimulating Hormone and luteinizing Hormone-chorionic gonadotropin Hormone Receptors), the FSHR is characterized by a large extracellular domain, where binding to FSH occurs, linked to the signal specificity subdomain or hinge region. This region is involved in ligand-stimulated Receptor activation whereas the seven transmembrane domain is associated with Receptor activation and transmision of the activation process to the intracellular loops comprised of amino acid sequences, which predicate coupling to effectors, interaction with adapter proteins, and triggering of downstream intracellular signaling. In this review, we describe the most important structural features of the FSHR intimately involved in regulation of FSHR function, including trafficking, dimerization and oligomerization, ligand binding, agonist-stimulated activation and signal transduction.
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Trafficking of the follitropin Receptor
Methods in Enzymology, 2013Co-Authors: Alfredo Ulloa-aguirre, James A Dias, George Bousfield, I. Huhtaniemi, Eric ReiterAbstract:The follitropin or Follicle-Stimulating Hormone Receptor (FSHR) belongs to a highly conserved subfamily of the G protein-coupled Receptor (GPCR) superfamily and is mainly expressed in specific cells in the gonads. As any other GPCR, the newly synthesized FSHR has to be correctly folded and processed in order to traffic to the cell surface plasma membrane and interact with its cognate ligand. In this chapter, we describe in detail the conditions and procedures used to study outward trafficking of the FSHR from the endoplasmic reticulum to the plasma membrane. We also describe some methods to analyze phosphorylation, beta-arrestin recruitment, internalization, and recycling of this particular Receptor, which have proved useful in our hands for dissecting its downward trafficking and fate following agonist stimulation.
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Increased Plasma Membrane Expression of Human Follicle-Stimulating Hormone Receptor by a Small Molecule Thienopyr(im)idine
Molecular and Cellular Endocrinology, 2009Co-Authors: Jo Ann Janovick, James A Dias, Alfredo Ulloa-aguirre, Guadalupe Maya-núñez, Ilpo Huhtaniemi, Pieter Verbost, P. Michael ConnAbstract:Abstract A thienopyr(im)idine (Org41841) activates the luteinizing Hormone (LH) Receptor but does not compete with the natural ligand binding site and does not show agonistic action on the Follicle-Stimulating Hormone Receptor (hFSHR) at sub- milli molar concentrations. When this drug is preincubated at sub- micro molar concentrations with host cells expressing the hFSHR, and then washed out, binding analysis and assessment of Receptor–effector coupling show that it increases plasma membrane expression of the hFSHR. Real-time PCR shows that this effect did not result from increased hFSHR mRNA accumulation. It is possible that Org41841 behaves as a pharmacoperone, a drug which increases the percentage of newly synthesized Receptor routing to the membrane. Like pharmacoperones for other Receptors, this drug was able to rescue a particular mutant hFSHR (A 189 V) associated with misrouting and endoplasmic reticulum retention, although other mutants could not be rescued. This is potentially the first member of the pharmacoperone drug class which binds at a site that is distinctive from the ligand binding site.
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Multiple facets of Follicle-Stimulating Hormone Receptor function
Endocrine, 2007Co-Authors: Alfredo Ulloa-aguirre, Ana Ma. Pasapera, Patricia Casas-gonzález, Teresa Zariñán, James A DiasAbstract:Follicle-Stimulating Hormone (FSH) is a glycoprotein Hormone produced by the anterior pituitary gland. This gonadotropin plays an essential role in reproduction. Its Receptor (FSHR) belongs to the superfamily of G protein-coupled Receptors (GPCR), specifically the family of rhodopsin-like Receptors. Agonist binding to the FSHR triggers the rapid activation of multiple signaling cascades, mainly the cAMP–adenylyl cyclase–protein kinase A cascade, that impact diverse biological effects of FSH in the gonads. As in other G protein-coupled Receptors, the several cytoplasmic domains of the FSHR are involved in signal transduction and termination of the FSH signal. Here we summarize some recent information on the signaling cascades activated by FSH as well as on the role of the intracytoplasmic domains of the FSHR in coupling to membrane and cytosolic proteins linked to key biological functions regulated by the FSH–FSHR system.
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Human follicle stimulating Hormone Receptor trafficking and Hormone binding sites in the amino terminus.
Molecular and Cellular Endocrinology, 2000Co-Authors: Cheryl A. Nechamen, James A DiasAbstract:Abstract Previous studies of the rat Follicle-Stimulating Hormone Receptor (rFSHR) demonstrated that the amino terminus is important in FSH binding and signal transduction. To define the structure–function correlates of this region, we prepared deletion and alanine scanning mutants of amino acids (a.a.) 9–30 in human FSHR (hFSHR). The deletion mutants ΔS9-S18, ΔK19-N30 and ΔS9-N30 failed to bind 125I-hFSH. Alanine substitution in the mutants 2HHRI5/2AAAA5, 7HCSNR11/7ACAAA11, 16QES18/16AAA18 and 19KVT21/19AAA21 increased the affinity of hFSHR for hFSH with equilibrium dissociation constants two to fivefold lower than wild type (wt) values. Signal transduction in 2HHRI5/2AAAA5 and 19KVT21/19AAA21 was similar to wt values, whereas 7HCSNR11/7ACAAA11 and 16QES18/16AAA18 showed a twofold lower accumulation of cAMP in response to hFSH than wt. These results indicate that these regions play a role in Hormone binding and signal transduction. In contrast, cells infected with mutants 12VFL14/12AAA14, 22EIPS25/22AAPA25 and 26DLPRN30/26AAPAA30 were incapable of binding 125I-hFSH even when solubilized with nonionic detergent. Flow cytometry indicated that hFSHR in 12VFL14/12AAA14, 22EIPS25/22AAPA25 and 26DLPRN30/26AAPAA30 was not present on the cell surface although the protein was expressed at high levels as determined by Western blotting. These results suggest that a discontinuous epitope in the N-terminus, likely stabilized by disulfide bonds and outside of the leucine-rich repeat domains, constitutes a Hormone binding site, membrane localization signal or both.
Alfredo Ulloa-aguirre - One of the best experts on this subject based on the ideXlab platform.
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Structure-Function Relationships of the Follicle-Stimulating Hormone Receptor
Frontiers in Endocrinology, 2018Co-Authors: Alfredo Ulloa-aguirre, Teresa Zariñán, Eduardo Jardón-valadez, Rubén Gutiérrez-sagal, James A DiasAbstract:The Follicle-Stimulating Hormone Receptor (FSHR) plays a crucial role in reproduction. This structurally complex Receptor belongs to the G-protein coupled Receptor (GPCR) superfamily of membrane Receptors. As with the other structurally similar glycoprotein Hormone Receptors (the thyroid-stimulating Hormone and luteinizing Hormone-chorionic gonadotropin Hormone Receptors), the FSHR is characterized by a large extracellular domain, where binding to FSH occurs, linked to the signal specificity subdomain or hinge region. This region is involved in ligand-stimulated Receptor activation whereas the seven transmembrane domain is associated with Receptor activation and transmision of the activation process to the intracellular loops comprised of amino acid sequences, which predicate coupling to effectors, interaction with adapter proteins, and triggering of downstream intracellular signaling. In this review, we describe the most important structural features of the FSHR intimately involved in regulation of FSHR function, including trafficking, dimerization and oligomerization, ligand binding, agonist-stimulated activation and signal transduction.
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The Follicle-Stimulating Hormone Receptor Asn680Ser polymorphism is associated with preterm birth in Hispanic women.
Journal of Maternal-fetal & Neonatal Medicine, 2017Co-Authors: Pablo Dominguez-lopez, Alfredo Ulloa-aguirre, Laura Diaz-cueto, Miguel Arechavaleta-velasco, Felipe Caldiño-soto, Fabian Arechavaleta-velascoAbstract:Objective: Recently, a study based on the analysis of accelerated evolution of related genes at birth identified the Follicle-Stimulating Hormone Receptor (FSHR) as a possible candidate for the dev...
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Trafficking of the follitropin Receptor
Methods in Enzymology, 2013Co-Authors: Alfredo Ulloa-aguirre, James A Dias, George Bousfield, I. Huhtaniemi, Eric ReiterAbstract:The follitropin or Follicle-Stimulating Hormone Receptor (FSHR) belongs to a highly conserved subfamily of the G protein-coupled Receptor (GPCR) superfamily and is mainly expressed in specific cells in the gonads. As any other GPCR, the newly synthesized FSHR has to be correctly folded and processed in order to traffic to the cell surface plasma membrane and interact with its cognate ligand. In this chapter, we describe in detail the conditions and procedures used to study outward trafficking of the FSHR from the endoplasmic reticulum to the plasma membrane. We also describe some methods to analyze phosphorylation, beta-arrestin recruitment, internalization, and recycling of this particular Receptor, which have proved useful in our hands for dissecting its downward trafficking and fate following agonist stimulation.
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Increased Plasma Membrane Expression of Human Follicle-Stimulating Hormone Receptor by a Small Molecule Thienopyr(im)idine
Molecular and Cellular Endocrinology, 2009Co-Authors: Jo Ann Janovick, James A Dias, Alfredo Ulloa-aguirre, Guadalupe Maya-núñez, Ilpo Huhtaniemi, Pieter Verbost, P. Michael ConnAbstract:Abstract A thienopyr(im)idine (Org41841) activates the luteinizing Hormone (LH) Receptor but does not compete with the natural ligand binding site and does not show agonistic action on the Follicle-Stimulating Hormone Receptor (hFSHR) at sub- milli molar concentrations. When this drug is preincubated at sub- micro molar concentrations with host cells expressing the hFSHR, and then washed out, binding analysis and assessment of Receptor–effector coupling show that it increases plasma membrane expression of the hFSHR. Real-time PCR shows that this effect did not result from increased hFSHR mRNA accumulation. It is possible that Org41841 behaves as a pharmacoperone, a drug which increases the percentage of newly synthesized Receptor routing to the membrane. Like pharmacoperones for other Receptors, this drug was able to rescue a particular mutant hFSHR (A 189 V) associated with misrouting and endoplasmic reticulum retention, although other mutants could not be rescued. This is potentially the first member of the pharmacoperone drug class which binds at a site that is distinctive from the ligand binding site.
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Multiple facets of Follicle-Stimulating Hormone Receptor function
Endocrine, 2007Co-Authors: Alfredo Ulloa-aguirre, Ana Ma. Pasapera, Patricia Casas-gonzález, Teresa Zariñán, James A DiasAbstract:Follicle-Stimulating Hormone (FSH) is a glycoprotein Hormone produced by the anterior pituitary gland. This gonadotropin plays an essential role in reproduction. Its Receptor (FSHR) belongs to the superfamily of G protein-coupled Receptors (GPCR), specifically the family of rhodopsin-like Receptors. Agonist binding to the FSHR triggers the rapid activation of multiple signaling cascades, mainly the cAMP–adenylyl cyclase–protein kinase A cascade, that impact diverse biological effects of FSH in the gonads. As in other G protein-coupled Receptors, the several cytoplasmic domains of the FSHR are involved in signal transduction and termination of the FSH signal. Here we summarize some recent information on the signaling cascades activated by FSH as well as on the role of the intracytoplasmic domains of the FSHR in coupling to membrane and cytosolic proteins linked to key biological functions regulated by the FSH–FSHR system.