Suppression of fertility in male mice by immunization against LH receptor

Rémy, Jean-Serge; Bozon, Véronique; Couture, Laurence; Goxe, Béatrice; Salesse, Roland; Garnier, Jean

doi:10.1016/0165-0378(93)90042-g

Cited by 18 publications

(16 citation statements)

References 14 publications

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“…This distinguishes the LH/CG receptor and other glycoprotein hormone receptors from all other seven-TM receptors, which have the high affinity ligand binding sites in the membrane-associated domain (6). Exon 11 of the LH/CG receptor encodes the membrane-associated domain, which is capable of low affinity hormone binding and receptor activation (5,7). This membrane-associated domain includes seven-TM helices joined together by three exoloops and three cytoloops.…”

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confidence: 99%

The Luteinizing Hormone/Chorionic Gonadotropin Receptor Has Distinct Transmembrane Conductors for cAMP and Inositol Phosphate Signals

Gilchrist

Ryu

et al. 1996

Journal of Biological Chemistry

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The luteinizing hormone/chorionic gonadotropin receptor is a member of the seven-transmembrane receptor family. It is coupled, presumably via G s and G q , to two signal pathways involving adenylyl cyclase/cAMP and phospholipase C/inositol phosphate (IP). Little is known about the events prior to G-protein coupling: for example, whether these signals are generated from a single or multiple independent origins and mechanisms, when and where they diverge, and how they are transduced. We report novel observations that the cAMP signal and the IP signal originate and diverge upstream of G-protein coupling. The LH/CG 1 receptor is a member of the seven-transmembrane (TM) receptor family and comprises two distinct functional domains consisting of the extracellular N-terminal half and the membrane-associated C-terminal half. These two domains are encoded by 11 exons (1, 2). Exons 1-10 encode the extracellular N-terminal domain, which alone is responsible for high affinity hormone binding (3)(4)(5). This distinguishes the LH/CG receptor and other glycoprotein hormone receptors from all other seven-TM receptors, which have the high affinity ligand binding sites in the membrane-associated domain (6). Exon 11 of the LH/CG receptor encodes the membrane-associated domain, which is capable of low affinity hormone binding and receptor activation (5, 7). This membrane-associated domain includes seven-TM helices joined together by three exoloops and three cytoloops.The LH/CG receptor is coupled to the adenylyl cyclase and PLC signal pathways, inducing the production of cAMP and inositol phosphates (IPs) as intracellular signal molecules (8). These signal molecules are produced when the receptor couples, presumably through G s and G q (9), to adenylyl cyclase and PLC, respectively (10). However, little is known about the events prior to G-protein coupling (6) (in particular, when more than one signal is involved). As a first step to lead discussion, several simple mechanisms are hypothesized for dual signals as shown in Fig. 1. Hormonal signal generation and transfer can be likened to an electrical circuit. Contact between the hormone and the receptor acts as an on/off signal switch and the receptor conducts the signal to the terminal cytodomain G-protein dock. Signals may be generated and transferred by single switch/single conductor, single switch/dual conductors, or dual switches/dual conductors. We will examine these models in light of the existing evidence.Recent investigations have identified several amino acids of the LH/CG receptor that are important for receptor activation (11)(12)(13)(14)(15)(16)(17)(18)(19). Most of these amino acids are present in cytoplasmic or TM domains. Only a few were found in the extracellular regions of the LH/CG receptor (11,12,(17)(18)(19). The added significance of extracellular amino acids in receptor activation is that they are near or at the hormone binding domain and could be involved in signal generation (6). Although their involvement in cAMP induction has been extensively examined, non...

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confidence: 99%

The Luteinizing Hormone/Chorionic Gonadotropin Receptor Has Distinct Transmembrane Conductors for cAMP and Inositol Phosphate Signals

Gilchrist

Ryu

et al. 1996

Journal of Biological Chemistry

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“…The resulting truncated exodomain lacking the endodomain was trapped within precursor AC P16582; sequences are numbered from Met1). The cDNAs encoding LHR and LHR cells and not expressed on the surface of mammalian cells (2,(8)(9)(10)(11)(12)25). However, when the trapped exodo-were prepared by digesting the original porcine LH receptor cDNA with XbaI and then blunt-ended.…”

Section: ) the Same Holds For Construction Of Recombinant Baculovimentioning

confidence: 99%

“…The LHR 298-696 virus was prepared by recombithe reconstitution of a functional split receptor at the cell surface with ligand-binding affinity and signal nation of AcNPV viral DNA and the pGm16 plasmid containing the LHR 298-696 cDNA. This cDNA was placed transduction potency similar to that of the full-length recombinant receptor and the natural receptor (25). under the control of the P10 promoter.…”

Section: ) the Same Holds For Construction Of Recombinant Baculovimentioning

confidence: 99%

“…We severed the LHR at the unique amino acid position 297, thus producing the exodomain porcine LH receptor cDNA (2) (accession number of porcine lutropin-choriogonadotropic hormone receptor and the endodomain 298-696 (25). The resulting truncated exodomain lacking the endodomain was trapped within precursor AC P16582; sequences are numbered from Met1).…”

Section: ) the Same Holds For Construction Of Recombinant Baculovimentioning

confidence: 99%

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Rescue of Intracellularly Trapped Lutropin Receptor Exodomain by Endodomain and Reconstitution of a Functional Membrane Receptor: Interaction between Exo- and Endodomains

Bozon¹,

Couture

Pajot‐Augy

et al. 2002

Protein Expression and Purification

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“…Active immunization of prepubertal male mice with baculovirus-expressed recombinant porcine LH receptor proteins corresponding to either 1-297 aa or 1-370 aa resulted in the decrease of testosterone levels and spermatogenesis. 42 The fertility of the immunized mice was reduced up to 75%.…”

Section: Veterinary Applications Of Gnrh-based Contraceptive Vaccinementioning

confidence: 99%

Milestones in contraceptive vaccines development and hurdles in their application

Gupta

Shrestha

Minhas

2013

Human Vaccines & Immunotherapeutics

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Suppression of fertility in male mice by immunization against LH receptor

Cited by 18 publications

References 14 publications

The Luteinizing Hormone/Chorionic Gonadotropin Receptor Has Distinct Transmembrane Conductors for cAMP and Inositol Phosphate Signals

The Luteinizing Hormone/Chorionic Gonadotropin Receptor Has Distinct Transmembrane Conductors for cAMP and Inositol Phosphate Signals

Rescue of Intracellularly Trapped Lutropin Receptor Exodomain by Endodomain and Reconstitution of a Functional Membrane Receptor: Interaction between Exo- and Endodomains

Milestones in contraceptive vaccines development and hurdles in their application

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