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Hervé Tostivint - One of the best experts on this subject based on the ideXlab platform.
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Data_Sheet_2_Characterization of Gonadotropin-Releasing Hormone (GnRH) Genes From Cartilaginous Fish: Evolutionary Perspectives.PDF
2018Co-Authors: Anne-laure Gaillard, Sylvie Mazan, Byrappa Venkatesh, Boon-hui Tay, Daniela Pérez I. Sirkin, Anne-gaëlle Lafont, Céline De Flori, Paula G. Vissio, Sylvie Dufour, Hervé TostivintAbstract:The neuropeptide gonadotropin-releasing hormone (GnRH) plays an important role in the control of reproductive functions. Vertebrates possess multiple GnRH forms that are classified into three main groups, namely GnRH1, GnRH2, and GnRH3. In order to gain more insights into the GnRH gene family in vertebrates, we sought to identify which paralogs of this family are present in cartilaginous fish. For this purpose, we searched the genomes and/or transcriptomes of three representative species of this group, the small-spotted catshark, Scyliorhinus canicula, the whale shark, Rhincodon typus and the elephant shark Callorhinchus milii. In each species, we report the identification of three GnRH genes. In catshark and whale shark, phylogenetic and synteny analysis showed that these three genes correspond to GnRH1, GnRH2, and GnRH3. In both species, GnRH1 was found to encode a novel form of GnRH whose primary structure was determined as follows: QHWSFDLRPG. In elephant shark, the three genes correspond to GnRH1a and GnRH1b, two copies of the GnRH1 gene, plus GnRH2. 3D structure prediction of the chondrichthyan GnRH-associated peptides (GAPs) revealed that catshark GAP1, GAP2, and elephant shark GAP2 peptides exhibit a helix-loop-helix (HLH) structure. This structure observed for many osteichthyan GAP1 and GAP2, may convey GAP biological activity. This HLH structure could not be observed for elephant shark GAP1a and GAP1b. As for all other GAP3 described so far, no typical 3D HLH structure was observed for catshark nor whale shark GAP3. RT-PCR analysis revealed that GnRH1, GnRH2, and GnRH3 genes are differentially expressed in the catshark brain. GnRH1 mRNA appeared predominant in the diencephalon while GnRH2 and GnRH3 mRNAs seemed to be most abundant in the mesencephalon and telencephalon, respectively. Taken together, our results show that the GnRH gene repertoire of the vertebrate ancestor was entirely conserved in the chondrichthyan lineage but that the GnRH3 gene was probably lost in holocephali. They also suggest that the three GnRH neuronal systems previously described in the brain of bony vertebrates are also present in cartilaginous fish.
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Table_4_Characterization of Gonadotropin-Releasing Hormone (GnRH) Genes From Cartilaginous Fish: Evolutionary Perspectives.DOCX
2018Co-Authors: Anne-laure Gaillard, Sylvie Mazan, Byrappa Venkatesh, Boon-hui Tay, Daniela Pérez I. Sirkin, Anne-gaëlle Lafont, Céline De Flori, Paula G. Vissio, Sylvie Dufour, Hervé TostivintAbstract:The neuropeptide gonadotropin-releasing hormone (GnRH) plays an important role in the control of reproductive functions. Vertebrates possess multiple GnRH forms that are classified into three main groups, namely GnRH1, GnRH2, and GnRH3. In order to gain more insights into the GnRH gene family in vertebrates, we sought to identify which paralogs of this family are present in cartilaginous fish. For this purpose, we searched the genomes and/or transcriptomes of three representative species of this group, the small-spotted catshark, Scyliorhinus canicula, the whale shark, Rhincodon typus and the elephant shark Callorhinchus milii. In each species, we report the identification of three GnRH genes. In catshark and whale shark, phylogenetic and synteny analysis showed that these three genes correspond to GnRH1, GnRH2, and GnRH3. In both species, GnRH1 was found to encode a novel form of GnRH whose primary structure was determined as follows: QHWSFDLRPG. In elephant shark, the three genes correspond to GnRH1a and GnRH1b, two copies of the GnRH1 gene, plus GnRH2. 3D structure prediction of the chondrichthyan GnRH-associated peptides (GAPs) revealed that catshark GAP1, GAP2, and elephant shark GAP2 peptides exhibit a helix-loop-helix (HLH) structure. This structure observed for many osteichthyan GAP1 and GAP2, may convey GAP biological activity. This HLH structure could not be observed for elephant shark GAP1a and GAP1b. As for all other GAP3 described so far, no typical 3D HLH structure was observed for catshark nor whale shark GAP3. RT-PCR analysis revealed that GnRH1, GnRH2, and GnRH3 genes are differentially expressed in the catshark brain. GnRH1 mRNA appeared predominant in the diencephalon while GnRH2 and GnRH3 mRNAs seemed to be most abundant in the mesencephalon and telencephalon, respectively. Taken together, our results show that the GnRH gene repertoire of the vertebrate ancestor was entirely conserved in the chondrichthyan lineage but that the GnRH3 gene was probably lost in holocephali. They also suggest that the three GnRH neuronal systems previously described in the brain of bony vertebrates are also present in cartilaginous fish.
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Data_Sheet_7_Characterization of Gonadotropin-Releasing Hormone (GnRH) Genes From Cartilaginous Fish: Evolutionary Perspectives.DOCX
2018Co-Authors: Anne-laure Gaillard, Sylvie Mazan, Byrappa Venkatesh, Boon-hui Tay, Daniela Pérez I. Sirkin, Anne-gaëlle Lafont, Céline De Flori, Paula G. Vissio, Sylvie Dufour, Hervé TostivintAbstract:The neuropeptide gonadotropin-releasing hormone (GnRH) plays an important role in the control of reproductive functions. Vertebrates possess multiple GnRH forms that are classified into three main groups, namely GnRH1, GnRH2, and GnRH3. In order to gain more insights into the GnRH gene family in vertebrates, we sought to identify which paralogs of this family are present in cartilaginous fish. For this purpose, we searched the genomes and/or transcriptomes of three representative species of this group, the small-spotted catshark, Scyliorhinus canicula, the whale shark, Rhincodon typus and the elephant shark Callorhinchus milii. In each species, we report the identification of three GnRH genes. In catshark and whale shark, phylogenetic and synteny analysis showed that these three genes correspond to GnRH1, GnRH2, and GnRH3. In both species, GnRH1 was found to encode a novel form of GnRH whose primary structure was determined as follows: QHWSFDLRPG. In elephant shark, the three genes correspond to GnRH1a and GnRH1b, two copies of the GnRH1 gene, plus GnRH2. 3D structure prediction of the chondrichthyan GnRH-associated peptides (GAPs) revealed that catshark GAP1, GAP2, and elephant shark GAP2 peptides exhibit a helix-loop-helix (HLH) structure. This structure observed for many osteichthyan GAP1 and GAP2, may convey GAP biological activity. This HLH structure could not be observed for elephant shark GAP1a and GAP1b. As for all other GAP3 described so far, no typical 3D HLH structure was observed for catshark nor whale shark GAP3. RT-PCR analysis revealed that GnRH1, GnRH2, and GnRH3 genes are differentially expressed in the catshark brain. GnRH1 mRNA appeared predominant in the diencephalon while GnRH2 and GnRH3 mRNAs seemed to be most abundant in the mesencephalon and telencephalon, respectively. Taken together, our results show that the GnRH gene repertoire of the vertebrate ancestor was entirely conserved in the chondrichthyan lineage but that the GnRH3 gene was probably lost in holocephali. They also suggest that the three GnRH neuronal systems previously described in the brain of bony vertebrates are also present in cartilaginous fish.
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Characterization of Gonadotropin-Releasing Hormone (GnRH) Genes From Cartilaginous Fish: Evolutionary Perspectives
Frontiers in Neuroscience, 2018Co-Authors: Anne-laure Gaillard, Sylvie Mazan, Byrappa Venkatesh, Boon-hui Tay, Anne-gaëlle Lafont, Céline De Flori, Paula G. Vissio, Sylvie Dufour, Daniela Pérez Sirkin, Hervé TostivintAbstract:The neuropeptide gonadotropin-releasing hormone (GnRH) plays an important role in the control of reproductive functions. Vertebrates possess multiple GnRH forms that are classified into three main groups, namely GnRH1, GnRH2, and GnRH3. In order to gain more insights into the GnRH gene family in vertebrates, we sought to identify which paralogs of this family are present in cartilaginous fish. For this purpose, we searched the genomes and/or transcriptomes of three representative species of this group, the small-spotted catshark, Scyliorhinus canicula, the whale shark, Rhincodon typus and the elephant shark Callorhinchus milii. In each species, we report the identification of three GnRH genes. In catshark and whale shark, phylogenetic and synteny analysis showed that these three genes correspond to GnRH1, GnRH2, and GnRH3. In both species, GnRH1 was found to encode a novel form of GnRH whose primary structure was determined as follows: QHWSFDLRPG. In elephant shark, the three genes correspond to GnRH1a and GnRH1b, two copies of the GnRH1 gene, plus GnRH2. 3D structure prediction of the chondrichthyan GnRH-associated peptides (GAPs) revealed that catshark GAP1, GAP2, and elephant shark GAP2 peptides exhibit a helix-loop-helix (HLH) structure. This structure observed for many osteichthyan GAP1 and GAP2, may convey GAP biological activity. This HLH structure could not be observed for elephant shark GAP1a and GAP1b. As for all other GAP3 described so far, no typical 3D HLH structure was observed for catshark nor whale shark GAP3. RT-PCR analysis revealed that GnRH1, GnRH2, and GnRH3 genes are differentially expressed in the catshark brain. GnRH1 mRNA appeared predominant in the diencephalon while GnRH2 and GnRH3 mRNAs seemed to be most abundant in the mesencephalon and telencephalon, respectively. Taken together, our results show that the GnRH gene repertoire of the vertebrate ancestor was entirely conserved in the chondrichthyan lineage but that the GnRH3 gene was probably lost in holocephali. They also suggest that the three GnRH neuronal systems previously described in the brain of bony vertebrates are also present in cartilaginous fish.
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Image_1_Characterization of Gonadotropin-Releasing Hormone (GnRH) Genes From Cartilaginous Fish: Evolutionary Perspectives.TIFF
2018Co-Authors: Anne-laure Gaillard, Sylvie Mazan, Byrappa Venkatesh, Boon-hui Tay, Daniela Pérez I. Sirkin, Anne-gaëlle Lafont, Céline De Flori, Paula G. Vissio, Sylvie Dufour, Hervé TostivintAbstract:The neuropeptide gonadotropin-releasing hormone (GnRH) plays an important role in the control of reproductive functions. Vertebrates possess multiple GnRH forms that are classified into three main groups, namely GnRH1, GnRH2, and GnRH3. In order to gain more insights into the GnRH gene family in vertebrates, we sought to identify which paralogs of this family are present in cartilaginous fish. For this purpose, we searched the genomes and/or transcriptomes of three representative species of this group, the small-spotted catshark, Scyliorhinus canicula, the whale shark, Rhincodon typus and the elephant shark Callorhinchus milii. In each species, we report the identification of three GnRH genes. In catshark and whale shark, phylogenetic and synteny analysis showed that these three genes correspond to GnRH1, GnRH2, and GnRH3. In both species, GnRH1 was found to encode a novel form of GnRH whose primary structure was determined as follows: QHWSFDLRPG. In elephant shark, the three genes correspond to GnRH1a and GnRH1b, two copies of the GnRH1 gene, plus GnRH2. 3D structure prediction of the chondrichthyan GnRH-associated peptides (GAPs) revealed that catshark GAP1, GAP2, and elephant shark GAP2 peptides exhibit a helix-loop-helix (HLH) structure. This structure observed for many osteichthyan GAP1 and GAP2, may convey GAP biological activity. This HLH structure could not be observed for elephant shark GAP1a and GAP1b. As for all other GAP3 described so far, no typical 3D HLH structure was observed for catshark nor whale shark GAP3. RT-PCR analysis revealed that GnRH1, GnRH2, and GnRH3 genes are differentially expressed in the catshark brain. GnRH1 mRNA appeared predominant in the diencephalon while GnRH2 and GnRH3 mRNAs seemed to be most abundant in the mesencephalon and telencephalon, respectively. Taken together, our results show that the GnRH gene repertoire of the vertebrate ancestor was entirely conserved in the chondrichthyan lineage but that the GnRH3 gene was probably lost in holocephali. They also suggest that the three GnRH neuronal systems previously described in the brain of bony vertebrates are also present in cartilaginous fish.
Michiya Matsuyama - One of the best experts on this subject based on the ideXlab platform.
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molecular characterization and functional analysis of pituitary gnrh receptor in a commercial scombroid fish chub mackerel scomber japonicus
General and Comparative Endocrinology, 2017Co-Authors: Sanny David Pacheco Lumayno, Hirofumi Ohga, Sethu Selvaraj, Mitsuo Nyuji, Akihiko Yamaguchi, Michiya MatsuyamaAbstract:The gonadotropin-releasing hormone (GnRH) is essential during pubertal onset, for its regulation of the synthesis and release of pituitary gonadotropins. Its action is mediated by GnRH receptors (GNRHRs) in the pituitary gonadotrophs. Our previous study demonstrated that the chub mackerel brain expresses three GnRH forms (gnrh1, gnrh2, and gnrh3), and that only GnRH1 neurons innervate anterior pituitary regions. Furthermore, chub mackerel gnrh1 mRNA exhibited a significant increase at pubertal onset. The present study aimed to isolate the functional GNRHR form involved in chub mackerel puberty. The open reading frame of our cloned receptor encodes 428 amino acids and contains seven transmembrane domains. Phylogenetic analysis also indicated clustering with other teleost-type IIB GNRHRs, mainly those involved in reproduction. Reporter gene assay results showed that all four synthetic peptides (GnRH1, GnRH2, GnRH3, and GnRH analogue) bind to the cloned receptor. Three deduced GnRH ligands stimulated luteinizing hormone (LH) release from cultured pituitary cells in vitro. Receptor gene expression was mainly detected in the pituitary and showed an increasing trend in the developing gonadal stages of both sexes during the pubertal process; this process was synchronous with previous studies of follicle-stimulating hormone beta (fshβ) and lhβ gene expression in chub mackerel. These results suggest that the cloned receptor is likely involved in the regulation of pubertal onset in this species. Therefore, we have designated the receptor cmGNRHR1.
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expression changes of mrnas encoding kisspeptins and their receptors and gonadotropin releasing hormones during early development and gonadal sex differentiation periods in the brain of chub mackerel scomber japonicus
General and Comparative Endocrinology, 2015Co-Authors: Sethu Selvaraj, Hirofumi Ohga, Akihiko Yamaguchi, Hajime Kitano, Michiya MatsuyamaAbstract:Abstract In recent years, brain kisspeptin system has been shown to be involved in diverse reproductive function, including sexual differentiation in vertebrates. Our previous reports demonstrated that the chub mackerel ( Scomber japonicus ) brain expresses two kisspeptin ( kiss1 , kiss2 ), two kisspeptin receptor ( kissr1 , kissr2 ) and three gonadotropin-releasing hormone ( gnrh1 , gnrh2 , gnrh3 ) genes. In the present study, using quantitative real-time PCR (qRT-PCR) assays, we analysed expression changes of these genes during early development (0–30 dphs) and gonadal sex differentiation periods (37–60 dphs). Absolute expression level of kiss – kissr – gnrh in the whole head was higher between 0 and 15 dphs, in comparison to later developmental periods. Histological analyses revealed presence of sexually differentiated males and females with testicular and ovarian features at 37, 45, and 60 dphs. In both males and females, kiss2 , kissr1 , and kissr2 levels were higher at 37 dph, in comparison to 45 and 60 dphs, with kiss1 showing no significant differences. Levels of all three gnrh mRNAs were higher at 45 dph, in comparison to 60 dph. Changes in the expression level of kiss – kissr – gnrh mRNAs in different brain regions of sexually differentiated males and females indicated differences in their regional distribution. These results suggest possible involvement of Kiss–KissR–GnRH systems during early development and gonadal sex differentiation in the chub mackerel.
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molecular cloning and expression analysis of a gnrh like dodecapeptide in the swordtip squid loligo edulis
Zoological Science, 2009Co-Authors: Chinari Onitsuka, Akihiko Yamaguchi, Hikoichirou Kanamaru, Shin Oikawa, Tatsusuke Takeda, Michiya MatsuyamaAbstract:In vertebrates, gonadotropin-releasing hormone (GnRH), which is synthesized in the brain, is a key peptide involved in gonadal maturation regulated by the brain-pituitary-gonadal axis. GnRH isoforms and their primary structures have recently been determined in two species of non-chordates, the octopus (Octopus vulgaris) and sea hare (Aplysia californica), which are mollusks. Octopus and sea hare GnRHs are dodecapeptides that contain the structural core of chordate GnRH; however, chordate GnRHs, including tunicate GnRH, are decapeptides. In this study, we examined a GnRHlike peptide in the swordtip squid, Loligo edulis, to provide information on the structural evolution of GnRH in non-chordates. We isolated the full-length cDNA of a GnRH-like molecule from the central nervous system (CNS) of the squid. The open reading frame of this cDNA encodes a protein of 90 amino acids, which consists of a putative signal peptide, a GnRH dodecapeptide, a processing site, and a GnRH-associated peptide. This architecture is generally conserved in chordates. Compared to octopus GnRH, Squid GnRH is identical in the deduced amino acid sequence of the peptide, and 80.5% similar in base sequence. In a phylogenetic analysis, prepro-GnRHs of octopus, sea hare, and squid were segregated from all chordate prepro-GnRHs, in a group designated GnRH5. The squid prepro-GnRH mRNA was expressed mainly in the CNS. This study is the first report of GnRH cDNA cloning in squid and the third in non-chordates.
Ursula B Kaiser - One of the best experts on this subject based on the ideXlab platform.
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differential regulation of gonadotropin subunit gene promoter activity by pulsatile gonadotropin releasing hormone gnrh in perifused lβt2 cells role of gnrh receptor concentration
Endocrinology, 2003Co-Authors: Gregoy Y Bedecarrats, Ursula B KaiserAbstract:The pulsatile release of GnRH by the hypothalamus is required to stimulate the pituitary-gonadal axis, and variations in GnRH pulse frequency are associated with differential synthesis and release of LH and FSH by pituitary gonadotropes. How gonadotropes differentiate between GnRH pulse frequencies and subsequently differentially regulate the expression of the LH beta and FSH beta genes remains to be determined. In the present study, using a perifusion system that allows us to replicate the GnRH pulsatility occurring in vivo, we have systematically characterized the effects of varying GnRH pulse frequencies on LH beta, FSH beta, alpha, and GnRH receptor (GNRHR) gene promoter stimulation in L beta T2 cells. We demonstrate that LH beta gene promoter activity is stimulated to the greatest extent at higher GnRH pulse frequencies, whereas the FSH beta gene promoter is preferentially stimulated at lower GnRH pulse frequencies, reflecting previous observations in primary rat pituitary cells in vivo and in vitro. By measuring GnRH binding, we demonstrate that cell-surface GNRHR number is increased at higher frequencies of pulsatile GnRH and that this increase precedes the differential regulation of LH beta and FSH beta gene promoter activity. To test the role of GNRHR number in mediating the differential effects of pulsatile GnRH, the rat GNRHR was overexpressed in L beta T2 cells, and the response to pulsatile GnRH was again assessed. Interestingly, although overexpression of GNRHR had no effect on the frequency-dependent regulation of LH beta, the induction of FSH beta gene promoter activity by pulsatile GnRH was reduced, and frequency dependence was abrogated. Our results demonstrate that L beta T2 cells represent a suitable model for the study of the differential regulation of gonadotropin subunit gene expression by pulsatile GnRH. Furthermore, our studies indicate that cell-surface GNRHR density is a critical mediator of this differential regulation.
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Two common naturally occurring mutations in the human gonadotropin-releasing hormone (GnRH) receptor have differential effects on gonadotropin gene expression and on GnRH-mediated signal transduction
Journal of Clinical Endocrinology and Metabolism, 2003Co-Authors: Gregoy Y Bedecarrats, Katja D. Linher, Ursula B KaiserAbstract:Studies of naturally occurring human GnRH receptor (GNRHR) mutants may provide a useful approach to dissecting the signal transduction pathways involved in mediating the effects of GnRH. We have analyzed two common mutations in the GNRHR, corresponding to amino acid substitutions Gln106Arg and Arg262Gln, for their effects on the stimulation of gonadotropin subunit and GNRHR gene expression by GnRH. Despite similar impairment of GnRH-stimulated inositol phosphate production, dose-response analyses indicated that Gln106Arg and Arg262Gln both reduced the sensitivity of the FSH beta gene promoter to a greater extent than LH beta or alpha GSU, suggesting the involvement of more than one signaling pathway. Furthermore, although the sensitivities of the LH beta and FSH beta gene promoters to GnRH were similarly affected by both mutants, alpha GSU sensitivity was decreased to a greater extent by Arg262Gln than by Gln106Arg. Similarly, GNRHR gene promoter sensitivity was significantly reduced only by Arg262Gln. To further characterize the differential downstream effects of these mutant GNRHRs, we investigated their effects on additional signal transduction pathways. The mutant receptors differentially affected GnRH-mediated activation of the ERK pathway and GnRH stimulation of cAMP response element-mediated transcription. These results indicate that measurement of inositol phosphate production alone may not be adequate for assessing mutant GNRHR function and additional signal transduction pathways may better reflect physiologically relevant effects. The differential stimulation of LH beta, FSH beta, and alpha GSU gene expression may contribute to the varied phenotypes observed among patients harboring these mutations.
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direct binding of ap 1 fos jun proteins to a smad binding element facilitates both gonadotropin releasing hormone gnrh and activin mediated transcriptional activation of the mouse gnrh receptor gene
Journal of Biological Chemistry, 2002Co-Authors: Errol R Norwitz, Lisa B Spiryda, Joong Shin Park, Kyeonghoon Jeong, Elizabeth A Mcgee, Ursula B KaiserAbstract:The response of pituitary gonadotropes to gonadotropin-releasing hormone (GnRH) correlates directly with the concentration of GnRH receptors (GNRHR) on the cell surface, which is mediated in part at the level of gene expression. Several factors are known to affect expression of the mouse GNRHR (mGNRHR) gene, including GnRH and activin. We have previously shown that activin augments GnRH-mediated transcriptional activation of mGNRHR gene, and that region −387/−308 appears to be necessary to mediate this effect. This region contains two overlapping cis-regulatory elements of interest: GNRHR activating sequence (GRAS) and a putative SMAD-binding element (SBE). This study investigates the role of these elements and their cognate transcription factors in transactivation of the mGNRHR gene. Transfection studies confirm the presence of GnRH- and activin-response elements within −387/−308 of mGNRHR gene promoter. Competition electrophoretic mobility shift assay experiments using −335/−312 as probe and αT3–1 nuclear extract or SMAD, Jun, and Fos proteins demonstrate direct binding of AP-1 (Fos/Jun) protein complexes to −327/−322 and SMAD proteins to −329/−328. Further transfection studies using mutant constructs of these cis-regulatory elements confirm that both are functionally important. These data define a novel cis-regulatory element comprised of an overlapping SBE and newly characterized non-consensus AP-1 binding sequence that integrates the stimulatory transcriptional effects of both GnRH and activin on the mGNRHR gene.
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studies of gonadotropin releasing hormone gnrh action using gnrh receptor expressing pituitary cell lines
Endocrine Reviews, 1997Co-Authors: Ursula B Kaiser, Michael P Conn, William W ChinAbstract:I. Introduction II. GNRHR Structure Analysis III. Studies of GnRH Action in αT3-1 Cells A. Derivation of αT3-1 cells B. Characterization of αT3-1 cells C. GnRH binding D. GNRHR regulation 1. Homologous regulation by GnRH 2. Regulation by gonadal steroid hormones 3. Regulation by gonadal peptides 4. Regulation by second messenger activators E. Intracellular second messengers 1. G protein coupling 2. Inositol phosphates 3. Intracellular calcium 4. Protein kinase C 5. cAMP 6. Mitogen-activated protein kinases F. α-Subunit gene expression 1. Cell-specific expression 2. GnRH-stimulated expression G. Desensitization H. Summary of GnRH action in αT3-1 cells IV. Studies of GnRH Action in GH3 Cells Transfected with the GnRH Receptor (GGH3 Cells) A. Derivation of GH3 cells B. Characterization of GH3 cells C. Derivation of GH3 cells transfected with the GNRHR (GGH3 cells) D. GnRH binding E. GNRHR regulation F. Intracellular second messengers 1. G protein coupling 2. Inositol phosphates 3. cAMP G. Regulation of secre...
Liliane Schoofs - One of the best experts on this subject based on the ideXlab platform.
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corazonin signaling integrates energy homeostasis and lunar phase to regulate aspects of growth and sexual maturation in platynereis
Proceedings of the National Academy of Sciences of the United States of America, 2020Co-Authors: Gabriele Andreatta, Caroline Broyart, Charline Borghgraef, Karim Vadiwala, V V Kozin, Alessandra Polo, Andrea Bileck, Isabel Beets, Liliane Schoofs, Christopher GernerAbstract:The molecular mechanisms by which animals integrate external stimuli with internal energy balance to regulate major developmental and reproductive events still remain enigmatic. We investigated this aspect in the marine bristleworm, Platynereis dumerilii, a species where sexual maturation is tightly regulated by both metabolic state and lunar cycle. Our specific focus was on ligands and receptors of the gonadotropin-releasing hormone (GnRH) superfamily. Members of this superfamily are key in triggering sexual maturation in vertebrates but also regulate reproductive processes and energy homeostasis in invertebrates. Here we show that 3 of the 4 gnrh-like (gnrhl) preprohormone genes are expressed in specific and distinct neuronal clusters in the Platynereis brain. Moreover, ligand-receptor interaction analyses reveal a single Platynereis corazonin receptor (CrzR) to be activated by CRZ1/GnRHL1, CRZ2/GnRHL2, and GnRHL3 (previously classified as AKH1), whereas 2 AKH-type hormone receptors (GNRHR1/AKHR1 and GNRHR2/AKHR2) respond only to a single ligand (GnRH2/GnRHL4). Crz1/gnrhl1 exhibits a particularly strong up-regulation in sexually mature animals, after feeding, and in specific lunar phases. Homozygous crz1/gnrhl1 knockout animals exhibit a significant delay in maturation, reduced growth, and attenuated regeneration. Through a combination of proteomics and gene expression analysis, we identify enzymes involved in carbohydrate metabolism as transcriptional targets of CRZ1/GnRHL1 signaling. Our data suggest that Platynereis CRZ1/GnRHL1 coordinates glycoprotein turnover and energy homeostasis with growth and sexual maturation, integrating both metabolic and developmental demands with the worm's monthly cycle.
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adipokinetic hormone signaling through the gonadotropin releasing hormone receptor modulates egg laying in caenorhabditis elegans
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Marleen Lindemans, Feng Liu, Tom Janssen, Steven J Husson, Inge Mertens, Gerd Gade, Liliane SchoofsAbstract:In mammals, hypothalamic gonadotropin-releasing hormone (GnRH) is a neuropeptide that stimulates the release of gonadotropins from the anterior pituitary. The existence of a putative functional equivalent of this reproduction axis in protostomian invertebrates has been a matter of debate. In this study, the ligand for the GnRH receptor in the nematode Caenorhabditis elegans (Ce-GNRHR) was found using a bioinformatics approach. The peptide and its precursor are reminiscent of both insect adipokinetic hormones and GnRH-preprohormone precursors from tunicates and higher vertebrates. We cloned the AKH-GnRH-like preprohormone and the Ce-GNRHR and expressed the GPCR in HEK293T cells. The GNRHR was activated by the C. elegans AKH-GnRH-like peptide (EC50 = 150 nM) and by Drosophila AKH and other nematode AKH-GnRHs that we found in EST databases. Analogous to both insect AKH receptor and vertebrate GnRH receptor signaling, Ce-AKH-GnRH activated its receptor through a Gαq protein with Ca2+ as a second messenger. Gene silencing of Ce-GNRHR, Ce-AKH-GnRH, or both resulted in a delay in the egg-laying process, comparable to a delay in puberty in mammals lacking a normal dose of GnRH peptide or with a mutated GnRH precursor or receptor gene. The present data support the view that the AKH-GnRH signaling system probably arose very early in metazoan evolution and that its role in reproduction might have been developed before the divergence of protostomians and deuterostomians.
Weimin Zhang - One of the best experts on this subject based on the ideXlab platform.
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Data_Sheet_2_A Type IIb, but Not Type IIa, GnRH Receptor Mediates GnRH-Induced Release of Growth Hormone in the Ricefield Eel.PDF
2018Co-Authors: Dong Chen, Wei Yang, Shiying Han, Huiyi Yang, Xin Cen, Jiang Liu, Lihong Zhang, Weimin ZhangAbstract:Multiple gonadotropin-releasing hormone receptors (GNRHRs) are present in vertebrates, but their differential physiological relevances remain to be clarified. In the present study, we identified three GnRH ligands GnRH1 (pjGnRH), GnRH2 (cGnRH-II), and GnRH3 (sGnRH) from the brain, and two GnRH receptors GNRHR1 (GNRHR IIa) and GNRHR2 (GNRHR IIb) from the pituitary of the ricefield eel Monopterus albus. GnRH1 and GnRH3 but not GnRH2 immunoreactive neurons were detected in the pre-optic area, hypothalamus, and pituitary, suggesting that GnRH1 and GnRH3 may exert hypophysiotropic roles in ricefield eels. GNRHR1 mRNA was mainly detected in the pituitary, whereas GNRHR2 mRNA broadly in tissues of both females and males. In the pituitary, GNRHR1 and GNRHR2 immunoreactive cells were differentially distributed, with GNRHR1 immunoreactive cells mainly in peripheral areas of the adenohypophysis whereas GNRHR2 immunoreactive cells in the multicellular layers of adenohypophysis adjacent to the neurohypophysis. Dual-label fluorescent immunostaining showed that GNRHR2 but not GNRHR1 was localized to somatotropes, and all somatotropes are GNRHR2-positive cells and vice versa at all stages examined. GnRH1 and GnRH3 were shown to stimulate growth hormone (Gh) release from primary culture of pituitary cells, and to decrease Gh contents in the pituitary of ricefield eels 12 h post injection. GnRH1 and GnRH3 stimulated Gh release probably via PLC/IP3/PKC and Ca2+ pathways. These results, as a whole, suggested that GnRHs may bind to GNRHR2 but not GNRHR1 to trigger Gh release in ricefield eels, and provided novel information on differential roles of multiple GnRH receptors in vertebrates.
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Data_Sheet_10_A Type IIb, but Not Type IIa, GnRH Receptor Mediates GnRH-Induced Release of Growth Hormone in the Ricefield Eel.PDF
2018Co-Authors: Dong Chen, Wei Yang, Shiying Han, Huiyi Yang, Xin Cen, Jiang Liu, Lihong Zhang, Weimin ZhangAbstract:Multiple gonadotropin-releasing hormone receptors (GNRHRs) are present in vertebrates, but their differential physiological relevances remain to be clarified. In the present study, we identified three GnRH ligands GnRH1 (pjGnRH), GnRH2 (cGnRH-II), and GnRH3 (sGnRH) from the brain, and two GnRH receptors GNRHR1 (GNRHR IIa) and GNRHR2 (GNRHR IIb) from the pituitary of the ricefield eel Monopterus albus. GnRH1 and GnRH3 but not GnRH2 immunoreactive neurons were detected in the pre-optic area, hypothalamus, and pituitary, suggesting that GnRH1 and GnRH3 may exert hypophysiotropic roles in ricefield eels. GNRHR1 mRNA was mainly detected in the pituitary, whereas GNRHR2 mRNA broadly in tissues of both females and males. In the pituitary, GNRHR1 and GNRHR2 immunoreactive cells were differentially distributed, with GNRHR1 immunoreactive cells mainly in peripheral areas of the adenohypophysis whereas GNRHR2 immunoreactive cells in the multicellular layers of adenohypophysis adjacent to the neurohypophysis. Dual-label fluorescent immunostaining showed that GNRHR2 but not GNRHR1 was localized to somatotropes, and all somatotropes are GNRHR2-positive cells and vice versa at all stages examined. GnRH1 and GnRH3 were shown to stimulate growth hormone (Gh) release from primary culture of pituitary cells, and to decrease Gh contents in the pituitary of ricefield eels 12 h post injection. GnRH1 and GnRH3 stimulated Gh release probably via PLC/IP3/PKC and Ca2+ pathways. These results, as a whole, suggested that GnRHs may bind to GNRHR2 but not GNRHR1 to trigger Gh release in ricefield eels, and provided novel information on differential roles of multiple GnRH receptors in vertebrates.
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Table_1_A Type IIb, but Not Type IIa, GnRH Receptor Mediates GnRH-Induced Release of Growth Hormone in the Ricefield Eel.DOC
2018Co-Authors: Dong Chen, Wei Yang, Shiying Han, Huiyi Yang, Xin Cen, Jiang Liu, Lihong Zhang, Weimin ZhangAbstract:Multiple gonadotropin-releasing hormone receptors (GNRHRs) are present in vertebrates, but their differential physiological relevances remain to be clarified. In the present study, we identified three GnRH ligands GnRH1 (pjGnRH), GnRH2 (cGnRH-II), and GnRH3 (sGnRH) from the brain, and two GnRH receptors GNRHR1 (GNRHR IIa) and GNRHR2 (GNRHR IIb) from the pituitary of the ricefield eel Monopterus albus. GnRH1 and GnRH3 but not GnRH2 immunoreactive neurons were detected in the pre-optic area, hypothalamus, and pituitary, suggesting that GnRH1 and GnRH3 may exert hypophysiotropic roles in ricefield eels. GNRHR1 mRNA was mainly detected in the pituitary, whereas GNRHR2 mRNA broadly in tissues of both females and males. In the pituitary, GNRHR1 and GNRHR2 immunoreactive cells were differentially distributed, with GNRHR1 immunoreactive cells mainly in peripheral areas of the adenohypophysis whereas GNRHR2 immunoreactive cells in the multicellular layers of adenohypophysis adjacent to the neurohypophysis. Dual-label fluorescent immunostaining showed that GNRHR2 but not GNRHR1 was localized to somatotropes, and all somatotropes are GNRHR2-positive cells and vice versa at all stages examined. GnRH1 and GnRH3 were shown to stimulate growth hormone (Gh) release from primary culture of pituitary cells, and to decrease Gh contents in the pituitary of ricefield eels 12 h post injection. GnRH1 and GnRH3 stimulated Gh release probably via PLC/IP3/PKC and Ca2+ pathways. These results, as a whole, suggested that GnRHs may bind to GNRHR2 but not GNRHR1 to trigger Gh release in ricefield eels, and provided novel information on differential roles of multiple GnRH receptors in vertebrates.
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A Type IIb, but Not Type IIa, GnRH Receptor Mediates GnRH-Induced Release of Growth Hormone in the Ricefield Eel
Frontiers Media S.A., 2018Co-Authors: Dong Chen, Wei Yang, Shiying Han, Huiyi Yang, Xin Cen, Jiang Liu, Lihong Zhang, Weimin ZhangAbstract:Multiple gonadotropin-releasing hormone receptors (GNRHRs) are present in vertebrates, but their differential physiological relevances remain to be clarified. In the present study, we identified three GnRH ligands GnRH1 (pjGnRH), GnRH2 (cGnRH-II), and GnRH3 (sGnRH) from the brain, and two GnRH receptors GNRHR1 (GNRHR IIa) and GNRHR2 (GNRHR IIb) from the pituitary of the ricefield eel Monopterus albus. GnRH1 and GnRH3 but not GnRH2 immunoreactive neurons were detected in the pre-optic area, hypothalamus, and pituitary, suggesting that GnRH1 and GnRH3 may exert hypophysiotropic roles in ricefield eels. GNRHR1 mRNA was mainly detected in the pituitary, whereas GNRHR2 mRNA broadly in tissues of both females and males. In the pituitary, GNRHR1 and GNRHR2 immunoreactive cells were differentially distributed, with GNRHR1 immunoreactive cells mainly in peripheral areas of the adenohypophysis whereas GNRHR2 immunoreactive cells in the multicellular layers of adenohypophysis adjacent to the neurohypophysis. Dual-label fluorescent immunostaining showed that GNRHR2 but not GNRHR1 was localized to somatotropes, and all somatotropes are GNRHR2-positive cells and vice versa at all stages examined. GnRH1 and GnRH3 were shown to stimulate growth hormone (Gh) release from primary culture of pituitary cells, and to decrease Gh contents in the pituitary of ricefield eels 12 h post injection. GnRH1 and GnRH3 stimulated Gh release probably via PLC/IP3/PKC and Ca2+ pathways. These results, as a whole, suggested that GnRHs may bind to GNRHR2 but not GNRHR1 to trigger Gh release in ricefield eels, and provided novel information on differential roles of multiple GnRH receptors in vertebrates