Endogenously elevated androgens alter the developmental programming of the hypothalamic–pituitary axis in male mice

Autores
Gonzalez, Betina; Ratner, Laura Daniela; Di Giorgio, Noelia Paula; Poutanen, Matti; Huhtaniemi, Lipo T.; Calandra, Ricardo Saul; Lux, Victoria Adela R.; Rulli, Susana Beatriz
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Transgenic male mice that express human chorionic gonadotropin (hCG) α and β subunits constitutively hypersecrete hCG and produce elevated levels of androgens. The aim of this study was to characterize the hypothalamic–pituitary function of these transgenic (hCGαβ+) males by focusing on FSH regulation. Serum FSH levels and pituitary mRNA expression of Fshb, Lhb, Cga, Gnrhr and Esr1 were reduced, whereas Fst expression was increased in prepubertal hCGαβ+ males as compared with wild-type. In the hypothalamus, Cyp19a1 expression, GnRH concentration and ex-vivo GnRH pulsatility were elevated in prepubertal hCGαβ+ mice, whereas Kiss1 expression was decreased prepubertally and Gad67 expression was elevated neonatally. The effect of androgens on the developmental programming of the hypothalamic–pituitary axis of hCGαβ+ males was evaluated by perinatal and prepubertal antiandrogen (flutamide) administration. Our studies identified a critical window between gestational day 18 and postnatal day 14, during which chronically elevated androgens and/or their locally produced metabolites activate the hypothalamus and concomitantly shut-down the gonadotropin axis.
Fil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Ratner, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Di Giorgio, Noelia Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Poutanen, Matti. University of Turku; Finlandia
Fil: Huhtaniemi, Lipo T.. Imperial College London; Reino Unido. University of Turku; Finlandia
Fil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
HYPOTHALAMIC- PITUITARY AXIS
ANDROGEN
HUMAN CHORIONIC GONADOTROPHIN
FOLLICLE STIMULATING HORMONE
TRANSGENIC MODEL
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/243656

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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Endogenously elevated androgens alter the developmental programming of the hypothalamic–pituitary axis in male miceGonzalez, BetinaRatner, Laura DanielaDi Giorgio, Noelia PaulaPoutanen, MattiHuhtaniemi, Lipo T.Calandra, Ricardo SaulLux, Victoria Adela R.Rulli, Susana BeatrizHYPOTHALAMIC- PITUITARY AXISANDROGENHUMAN CHORIONIC GONADOTROPHINFOLLICLE STIMULATING HORMONETRANSGENIC MODELhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Transgenic male mice that express human chorionic gonadotropin (hCG) α and β subunits constitutively hypersecrete hCG and produce elevated levels of androgens. The aim of this study was to characterize the hypothalamic–pituitary function of these transgenic (hCGαβ+) males by focusing on FSH regulation. Serum FSH levels and pituitary mRNA expression of Fshb, Lhb, Cga, Gnrhr and Esr1 were reduced, whereas Fst expression was increased in prepubertal hCGαβ+ males as compared with wild-type. In the hypothalamus, Cyp19a1 expression, GnRH concentration and ex-vivo GnRH pulsatility were elevated in prepubertal hCGαβ+ mice, whereas Kiss1 expression was decreased prepubertally and Gad67 expression was elevated neonatally. The effect of androgens on the developmental programming of the hypothalamic–pituitary axis of hCGαβ+ males was evaluated by perinatal and prepubertal antiandrogen (flutamide) administration. Our studies identified a critical window between gestational day 18 and postnatal day 14, during which chronically elevated androgens and/or their locally produced metabolites activate the hypothalamus and concomitantly shut-down the gonadotropin axis.Fil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Ratner, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Di Giorgio, Noelia Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Poutanen, Matti. University of Turku; FinlandiaFil: Huhtaniemi, Lipo T.. Imperial College London; Reino Unido. University of Turku; FinlandiaFil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaElsevier Ireland2011-01info: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/pdfhttp://hdl.handle.net/11336/243656Gonzalez, Betina; Ratner, Laura Daniela; Di Giorgio, Noelia Paula; Poutanen, Matti; Huhtaniemi, Lipo T.; et al.; Endogenously elevated androgens alter the developmental programming of the hypothalamic–pituitary axis in male mice; Elsevier Ireland; Molecular and Cellular Endocrinology; 332; 1-2; 1-2011; 78-870303-7207CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0303720710004879info:eu-repo/semantics/altIdentifier/doi/10.1016/j.mce.2010.09.016info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:15:55Zoai:ri.conicet.gov.ar:11336/243656instacron: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:34982025-09-10 13:15:56.064CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Endogenously elevated androgens alter the developmental programming of the hypothalamic–pituitary axis in male mice
title Endogenously elevated androgens alter the developmental programming of the hypothalamic–pituitary axis in male mice
spellingShingle Endogenously elevated androgens alter the developmental programming of the hypothalamic–pituitary axis in male mice
Gonzalez, Betina
HYPOTHALAMIC- PITUITARY AXIS
ANDROGEN
HUMAN CHORIONIC GONADOTROPHIN
FOLLICLE STIMULATING HORMONE
TRANSGENIC MODEL
title_short Endogenously elevated androgens alter the developmental programming of the hypothalamic–pituitary axis in male mice
title_full Endogenously elevated androgens alter the developmental programming of the hypothalamic–pituitary axis in male mice
title_fullStr Endogenously elevated androgens alter the developmental programming of the hypothalamic–pituitary axis in male mice
title_full_unstemmed Endogenously elevated androgens alter the developmental programming of the hypothalamic–pituitary axis in male mice
title_sort Endogenously elevated androgens alter the developmental programming of the hypothalamic–pituitary axis in male mice
dc.creator.none.fl_str_mv Gonzalez, Betina
Ratner, Laura Daniela
Di Giorgio, Noelia Paula
Poutanen, Matti
Huhtaniemi, Lipo T.
Calandra, Ricardo Saul
Lux, Victoria Adela R.
Rulli, Susana Beatriz
author Gonzalez, Betina
author_facet Gonzalez, Betina
Ratner, Laura Daniela
Di Giorgio, Noelia Paula
Poutanen, Matti
Huhtaniemi, Lipo T.
Calandra, Ricardo Saul
Lux, Victoria Adela R.
Rulli, Susana Beatriz
author_role author
author2 Ratner, Laura Daniela
Di Giorgio, Noelia Paula
Poutanen, Matti
Huhtaniemi, Lipo T.
Calandra, Ricardo Saul
Lux, Victoria Adela R.
Rulli, Susana Beatriz
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HYPOTHALAMIC- PITUITARY AXIS
ANDROGEN
HUMAN CHORIONIC GONADOTROPHIN
FOLLICLE STIMULATING HORMONE
TRANSGENIC MODEL
topic HYPOTHALAMIC- PITUITARY AXIS
ANDROGEN
HUMAN CHORIONIC GONADOTROPHIN
FOLLICLE STIMULATING HORMONE
TRANSGENIC MODEL
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Transgenic male mice that express human chorionic gonadotropin (hCG) α and β subunits constitutively hypersecrete hCG and produce elevated levels of androgens. The aim of this study was to characterize the hypothalamic–pituitary function of these transgenic (hCGαβ+) males by focusing on FSH regulation. Serum FSH levels and pituitary mRNA expression of Fshb, Lhb, Cga, Gnrhr and Esr1 were reduced, whereas Fst expression was increased in prepubertal hCGαβ+ males as compared with wild-type. In the hypothalamus, Cyp19a1 expression, GnRH concentration and ex-vivo GnRH pulsatility were elevated in prepubertal hCGαβ+ mice, whereas Kiss1 expression was decreased prepubertally and Gad67 expression was elevated neonatally. The effect of androgens on the developmental programming of the hypothalamic–pituitary axis of hCGαβ+ males was evaluated by perinatal and prepubertal antiandrogen (flutamide) administration. Our studies identified a critical window between gestational day 18 and postnatal day 14, during which chronically elevated androgens and/or their locally produced metabolites activate the hypothalamus and concomitantly shut-down the gonadotropin axis.
Fil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Ratner, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Di Giorgio, Noelia Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Poutanen, Matti. University of Turku; Finlandia
Fil: Huhtaniemi, Lipo T.. Imperial College London; Reino Unido. University of Turku; Finlandia
Fil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description Transgenic male mice that express human chorionic gonadotropin (hCG) α and β subunits constitutively hypersecrete hCG and produce elevated levels of androgens. The aim of this study was to characterize the hypothalamic–pituitary function of these transgenic (hCGαβ+) males by focusing on FSH regulation. Serum FSH levels and pituitary mRNA expression of Fshb, Lhb, Cga, Gnrhr and Esr1 were reduced, whereas Fst expression was increased in prepubertal hCGαβ+ males as compared with wild-type. In the hypothalamus, Cyp19a1 expression, GnRH concentration and ex-vivo GnRH pulsatility were elevated in prepubertal hCGαβ+ mice, whereas Kiss1 expression was decreased prepubertally and Gad67 expression was elevated neonatally. The effect of androgens on the developmental programming of the hypothalamic–pituitary axis of hCGαβ+ males was evaluated by perinatal and prepubertal antiandrogen (flutamide) administration. Our studies identified a critical window between gestational day 18 and postnatal day 14, during which chronically elevated androgens and/or their locally produced metabolites activate the hypothalamus and concomitantly shut-down the gonadotropin axis.
publishDate 2011
dc.date.none.fl_str_mv 2011-01
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/11336/243656
Gonzalez, Betina; Ratner, Laura Daniela; Di Giorgio, Noelia Paula; Poutanen, Matti; Huhtaniemi, Lipo T.; et al.; Endogenously elevated androgens alter the developmental programming of the hypothalamic–pituitary axis in male mice; Elsevier Ireland; Molecular and Cellular Endocrinology; 332; 1-2; 1-2011; 78-87
0303-7207
CONICET Digital
CONICET
url http://hdl.handle.net/11336/243656
identifier_str_mv Gonzalez, Betina; Ratner, Laura Daniela; Di Giorgio, Noelia Paula; Poutanen, Matti; Huhtaniemi, Lipo T.; et al.; Endogenously elevated androgens alter the developmental programming of the hypothalamic–pituitary axis in male mice; Elsevier Ireland; Molecular and Cellular Endocrinology; 332; 1-2; 1-2011; 78-87
0303-7207
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0303720710004879
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.mce.2010.09.016
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
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application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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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