Lack of functional GABAB receptors alters Kiss1 , Gnrh1 and Gad1 mRNA expression in the medial basal hypothalamus at postnatal day 4

Autores
Di Giorgio, Noelia Paula; Catalano, Paolo Nicolás; Lopez, Paula Veronica; Gonzalez, Betina; Semaan, Sheila J.; Lopez, Gabriela Carina; Kauffman, Alexander S.; Rulli, Susana Beatriz; Somoza, Gustavo Manuel; Bettler, Bernhard; Libertun, Carlos; Lux, Victoria Adela R.
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Adult mice lacking functional GABA B receptors (GABA B1 KO) show altered Gnrh1 and Gad1 expressions in the preoptic area-anterior hypothalamus (POA-AH) and females display disruption of cyclicity and fertility. Here we addressed whether sexual differentiation of the brain and the proper wiring of the GnRH and kisspeptin systems were already disturbed in postnatal day 4 (PND4) GABA B1 KO mice. Methods: PND4 wild-type (WT) and GABA B1 KO mice of both sexes were sacrificed; tissues were collected to determine mRNA expression (qPCR), amino acids (HPLC), and hormones (RIA and/or IHC). Results: GnRH neuron number (IHC) did not differ among groups in olfactory bulbs or OVLT-POA. Gnrh1 mRNA (qPCR) in POA-AH was similar among groups. Gnrh1 mRNA in medial basal hypothalamus (MBH) was similar in WTs but was increased in GABA B1 KO females compared to GABA B1 KO males. Hypothalamic GnRH (RIA) was sexually different in WTs (males > females), but this sex difference was lost in GABA B1 KOs; the same pattern was observed when analyzing only the MBH, but not in the POA-AH. Arcuate nucleus Kiss1 mRNA (micropunch-qPCR) was higher in WT females than in WT males and GABA B1 KO females. Gad1 mRNA in MBH was increased in GABA B1 KO females compared to GABA B1 KO males. Serum LH and gonadal estradiol content were also increased in GABA B1 KOs. Conclusion: We demonstrate that GABA B Rs participate in the sexual differentiation of the ARC/MBH, because sex differences in several reproductive genes, such as Gad1 , Kiss1 and Gnrh1, are critically disturbed in GABA B1 KO mice at PND4, probably altering the organization and development of neural circuits governing the reproductive axis.
Fil: Di Giorgio, Noelia Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Catalano, Paolo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Lopez, Paula Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Semaan, Sheila J.. University Of California At Davis; Estados Unidos
Fil: Lopez, Gabriela Carina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); Argentina
Fil: Kauffman, Alexander S.. University Of California At San Diego; Estados Unidos
Fil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Somoza, Gustavo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); Argentina
Fil: Bettler, Bernhard. University of Basel; Suiza
Fil: Libertun, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Materia
Gaba B Receptors
Gnrh
Gaba
Kiss 1 Protein
Gonadotropins
Sex Steroids
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/7667
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/7667
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Lack of functional GABAB receptors alters Kiss1 , Gnrh1 and Gad1 mRNA expression in the medial basal hypothalamus at postnatal day 4Di Giorgio, Noelia PaulaCatalano, Paolo NicolásLopez, Paula VeronicaGonzalez, BetinaSemaan, Sheila J.Lopez, Gabriela CarinaKauffman, Alexander S.Rulli, Susana BeatrizSomoza, Gustavo ManuelBettler, BernhardLibertun, CarlosLux, Victoria Adela R.Gaba B ReceptorsGnrhGabaKiss 1 ProteinGonadotropinsSex Steroidshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Adult mice lacking functional GABA B receptors (GABA B1 KO) show altered Gnrh1 and Gad1 expressions in the preoptic area-anterior hypothalamus (POA-AH) and females display disruption of cyclicity and fertility. Here we addressed whether sexual differentiation of the brain and the proper wiring of the GnRH and kisspeptin systems were already disturbed in postnatal day 4 (PND4) GABA B1 KO mice. Methods: PND4 wild-type (WT) and GABA B1 KO mice of both sexes were sacrificed; tissues were collected to determine mRNA expression (qPCR), amino acids (HPLC), and hormones (RIA and/or IHC). Results: GnRH neuron number (IHC) did not differ among groups in olfactory bulbs or OVLT-POA. Gnrh1 mRNA (qPCR) in POA-AH was similar among groups. Gnrh1 mRNA in medial basal hypothalamus (MBH) was similar in WTs but was increased in GABA B1 KO females compared to GABA B1 KO males. Hypothalamic GnRH (RIA) was sexually different in WTs (males > females), but this sex difference was lost in GABA B1 KOs; the same pattern was observed when analyzing only the MBH, but not in the POA-AH. Arcuate nucleus Kiss1 mRNA (micropunch-qPCR) was higher in WT females than in WT males and GABA B1 KO females. Gad1 mRNA in MBH was increased in GABA B1 KO females compared to GABA B1 KO males. Serum LH and gonadal estradiol content were also increased in GABA B1 KOs. Conclusion: We demonstrate that GABA B Rs participate in the sexual differentiation of the ARC/MBH, because sex differences in several reproductive genes, such as Gad1 , Kiss1 and Gnrh1, are critically disturbed in GABA B1 KO mice at PND4, probably altering the organization and development of neural circuits governing the reproductive axis.Fil: Di Giorgio, Noelia Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Catalano, Paolo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Lopez, Paula Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Semaan, Sheila J.. University Of California At Davis; Estados UnidosFil: Lopez, Gabriela Carina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); ArgentinaFil: Kauffman, Alexander S.. University Of California At San Diego; Estados UnidosFil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Somoza, Gustavo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); ArgentinaFil: Bettler, Bernhard. University of Basel; SuizaFil: Libertun, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaKarger2013-12-31info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/7667Di Giorgio, Noelia Paula; Catalano, Paolo Nicolás; Lopez, Paula Veronica; Gonzalez, Betina; Semaan, Sheila J.; et al.; Lack of functional GABAB receptors alters Kiss1 , Gnrh1 and Gad1 mRNA expression in the medial basal hypothalamus at postnatal day 4; Karger; Neuroendocrinology; 98; 3; 31-12-2013; 212-2230028-38351423-0194enginfo:eu-repo/semantics/altIdentifier/doi/10.1159/000355631info:eu-repo/semantics/altIdentifier/url/http://www.karger.com/Article/FullText/355631info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915412/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:49Zoai:ri.conicet.gov.ar:11336/7667instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:59:49.77CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Lack of functional GABAB receptors alters Kiss1 , Gnrh1 and Gad1 mRNA expression in the medial basal hypothalamus at postnatal day 4
title Lack of functional GABAB receptors alters Kiss1 , Gnrh1 and Gad1 mRNA expression in the medial basal hypothalamus at postnatal day 4
spellingShingle Lack of functional GABAB receptors alters Kiss1 , Gnrh1 and Gad1 mRNA expression in the medial basal hypothalamus at postnatal day 4
Di Giorgio, Noelia Paula
Gaba B Receptors
Gnrh
Gaba
Kiss 1 Protein
Gonadotropins
Sex Steroids
title_short Lack of functional GABAB receptors alters Kiss1 , Gnrh1 and Gad1 mRNA expression in the medial basal hypothalamus at postnatal day 4
title_full Lack of functional GABAB receptors alters Kiss1 , Gnrh1 and Gad1 mRNA expression in the medial basal hypothalamus at postnatal day 4
title_fullStr Lack of functional GABAB receptors alters Kiss1 , Gnrh1 and Gad1 mRNA expression in the medial basal hypothalamus at postnatal day 4
title_full_unstemmed Lack of functional GABAB receptors alters Kiss1 , Gnrh1 and Gad1 mRNA expression in the medial basal hypothalamus at postnatal day 4
title_sort Lack of functional GABAB receptors alters Kiss1 , Gnrh1 and Gad1 mRNA expression in the medial basal hypothalamus at postnatal day 4
dc.creator.none.fl_str_mv Di Giorgio, Noelia Paula
Catalano, Paolo Nicolás
Lopez, Paula Veronica
Gonzalez, Betina
Semaan, Sheila J.
Lopez, Gabriela Carina
Kauffman, Alexander S.
Rulli, Susana Beatriz
Somoza, Gustavo Manuel
Bettler, Bernhard
Libertun, Carlos
Lux, Victoria Adela R.
author Di Giorgio, Noelia Paula
author_facet Di Giorgio, Noelia Paula
Catalano, Paolo Nicolás
Lopez, Paula Veronica
Gonzalez, Betina
Semaan, Sheila J.
Lopez, Gabriela Carina
Kauffman, Alexander S.
Rulli, Susana Beatriz
Somoza, Gustavo Manuel
Bettler, Bernhard
Libertun, Carlos
Lux, Victoria Adela R.
author_role author
author2 Catalano, Paolo Nicolás
Lopez, Paula Veronica
Gonzalez, Betina
Semaan, Sheila J.
Lopez, Gabriela Carina
Kauffman, Alexander S.
Rulli, Susana Beatriz
Somoza, Gustavo Manuel
Bettler, Bernhard
Libertun, Carlos
Lux, Victoria Adela R.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Gaba B Receptors
Gnrh
Gaba
Kiss 1 Protein
Gonadotropins
Sex Steroids
topic Gaba B Receptors
Gnrh
Gaba
Kiss 1 Protein
Gonadotropins
Sex Steroids
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Adult mice lacking functional GABA B receptors (GABA B1 KO) show altered Gnrh1 and Gad1 expressions in the preoptic area-anterior hypothalamus (POA-AH) and females display disruption of cyclicity and fertility. Here we addressed whether sexual differentiation of the brain and the proper wiring of the GnRH and kisspeptin systems were already disturbed in postnatal day 4 (PND4) GABA B1 KO mice. Methods: PND4 wild-type (WT) and GABA B1 KO mice of both sexes were sacrificed; tissues were collected to determine mRNA expression (qPCR), amino acids (HPLC), and hormones (RIA and/or IHC). Results: GnRH neuron number (IHC) did not differ among groups in olfactory bulbs or OVLT-POA. Gnrh1 mRNA (qPCR) in POA-AH was similar among groups. Gnrh1 mRNA in medial basal hypothalamus (MBH) was similar in WTs but was increased in GABA B1 KO females compared to GABA B1 KO males. Hypothalamic GnRH (RIA) was sexually different in WTs (males > females), but this sex difference was lost in GABA B1 KOs; the same pattern was observed when analyzing only the MBH, but not in the POA-AH. Arcuate nucleus Kiss1 mRNA (micropunch-qPCR) was higher in WT females than in WT males and GABA B1 KO females. Gad1 mRNA in MBH was increased in GABA B1 KO females compared to GABA B1 KO males. Serum LH and gonadal estradiol content were also increased in GABA B1 KOs. Conclusion: We demonstrate that GABA B Rs participate in the sexual differentiation of the ARC/MBH, because sex differences in several reproductive genes, such as Gad1 , Kiss1 and Gnrh1, are critically disturbed in GABA B1 KO mice at PND4, probably altering the organization and development of neural circuits governing the reproductive axis.
Fil: Di Giorgio, Noelia Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Catalano, Paolo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Lopez, Paula Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Semaan, Sheila J.. University Of California At Davis; Estados Unidos
Fil: Lopez, Gabriela Carina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); Argentina
Fil: Kauffman, Alexander S.. University Of California At San Diego; Estados Unidos
Fil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Somoza, Gustavo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); Argentina
Fil: Bettler, Bernhard. University of Basel; Suiza
Fil: Libertun, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
description Adult mice lacking functional GABA B receptors (GABA B1 KO) show altered Gnrh1 and Gad1 expressions in the preoptic area-anterior hypothalamus (POA-AH) and females display disruption of cyclicity and fertility. Here we addressed whether sexual differentiation of the brain and the proper wiring of the GnRH and kisspeptin systems were already disturbed in postnatal day 4 (PND4) GABA B1 KO mice. Methods: PND4 wild-type (WT) and GABA B1 KO mice of both sexes were sacrificed; tissues were collected to determine mRNA expression (qPCR), amino acids (HPLC), and hormones (RIA and/or IHC). Results: GnRH neuron number (IHC) did not differ among groups in olfactory bulbs or OVLT-POA. Gnrh1 mRNA (qPCR) in POA-AH was similar among groups. Gnrh1 mRNA in medial basal hypothalamus (MBH) was similar in WTs but was increased in GABA B1 KO females compared to GABA B1 KO males. Hypothalamic GnRH (RIA) was sexually different in WTs (males > females), but this sex difference was lost in GABA B1 KOs; the same pattern was observed when analyzing only the MBH, but not in the POA-AH. Arcuate nucleus Kiss1 mRNA (micropunch-qPCR) was higher in WT females than in WT males and GABA B1 KO females. Gad1 mRNA in MBH was increased in GABA B1 KO females compared to GABA B1 KO males. Serum LH and gonadal estradiol content were also increased in GABA B1 KOs. Conclusion: We demonstrate that GABA B Rs participate in the sexual differentiation of the ARC/MBH, because sex differences in several reproductive genes, such as Gad1 , Kiss1 and Gnrh1, are critically disturbed in GABA B1 KO mice at PND4, probably altering the organization and development of neural circuits governing the reproductive axis.
publishDate 2013
dc.date.none.fl_str_mv 2013-12-31
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/7667
Di Giorgio, Noelia Paula; Catalano, Paolo Nicolás; Lopez, Paula Veronica; Gonzalez, Betina; Semaan, Sheila J.; et al.; Lack of functional GABAB receptors alters Kiss1 , Gnrh1 and Gad1 mRNA expression in the medial basal hypothalamus at postnatal day 4; Karger; Neuroendocrinology; 98; 3; 31-12-2013; 212-223
0028-3835
1423-0194
url http://hdl.handle.net/11336/7667
identifier_str_mv Di Giorgio, Noelia Paula; Catalano, Paolo Nicolás; Lopez, Paula Veronica; Gonzalez, Betina; Semaan, Sheila J.; et al.; Lack of functional GABAB receptors alters Kiss1 , Gnrh1 and Gad1 mRNA expression in the medial basal hypothalamus at postnatal day 4; Karger; Neuroendocrinology; 98; 3; 31-12-2013; 212-223
0028-3835
1423-0194
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915412/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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eu_rights_str_mv openAccess
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dc.publisher.none.fl_str_mv Karger
publisher.none.fl_str_mv Karger
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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