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Enregistrement W1975970873 · doi:10.1074/jbc.m409616200

Repression of the Human Sex Hormone-binding Globulin Gene in Sertoli Cells by Upstream Stimulatory Transcription Factors

2004· article· en· W1975970873 sur OpenAlexaff
David M. Selva, Kevin Hogeveen, Geoffrey L. Hammond

Notice bibliographique

RevueJournal of Biological Chemistry · 2004
Typearticle
Langueen
DomaineMedicine
ThématiqueSperm and Testicular Function
Établissements canadiensUniversity of British ColumbiaBC Research (Canada)
Organismes subventionnairesnon disponible
Mots-clésSertoli cellPsychological repressionSex hormone-binding globulinGeneBiologyTranscription (linguistics)HormoneTranscription factorEndocrinologyInternal medicineCell biologyGeneticsGene expressionMedicineSpermatogenesisAndrogen

Résumé

récupéré en direct d'OpenAlex

Expression of the sex hormone-binding globulin gene (SHBG) in the liver produces SHBG, which transports sex steroids in the blood. In rodents, the SHBG gene is also expressed in Sertoli cells giving rise to the testicular androgen-binding protein, which is secreted into the seminiferous tubule where it presumably controls testosterone action. Evidence that the SHBG gene functions in this way in the human testis is lacking, and mice containing a human SHBG transgene (shbg4) under the control of its own promoter sequence are characterized by SHBG gene expression in the liver but not in the testis. A potential cis-element, defined as footprint 4 (FP4) within the human SHBG promoter, is absent in SHBG promoters of mammals that produce the testicular androgen-binding protein, and we have produced mice harboring a shbg4 transgene in which FP4 was deleted to evaluate its functional significance. Remarkably, these mice express the human SHBG transgene in the testis as as the SHBG within Sertoli of which human SHBG, and this was by and but not have also that the and FP4 in by of Sertoli and in by and that human SHBG in Sertoli cells FP4 within its Expression of the sex hormone-binding globulin gene (SHBG) in the liver produces SHBG, which transports sex steroids in the blood. In rodents, the SHBG gene is also expressed in Sertoli cells giving rise to the testicular androgen-binding protein, which is secreted into the seminiferous tubule where it presumably controls testosterone action. Evidence that the SHBG gene functions in this way in the human testis is lacking, and mice containing a human SHBG transgene (shbg4) under the control of its own promoter sequence are characterized by SHBG gene expression in the liver but not in the testis. A potential cis-element, defined as footprint 4 (FP4) within the human SHBG promoter, is absent in SHBG promoters of mammals that produce the testicular androgen-binding protein, and we have produced mice harboring a shbg4 transgene in which FP4 was deleted to evaluate its functional significance. Remarkably, these mice express the human SHBG transgene in the testis as as the SHBG within Sertoli of which human SHBG, and this was by and but not have also that the and FP4 in by of Sertoli and in by and that human SHBG in Sertoli cells FP4 within its sex hormone-binding globulin (SHBG) SHBG, sex hormone-binding footprint SHBG, sex hormone-binding footprint is produced by and it transports sex steroids in the and to A and as SHBG was in the testis and of and protein, which is to as the testicular androgen-binding protein, to the of the that SHBG A of that androgen-binding by Sertoli cells in is by and but not testosterone this is secreted into the seminiferous and to the where it is by cells it is to to cells within the and of of a in human testis the as SHBG to the that SHBG expression and in the human testis that in human testis are by SHBG, and it to the SHBG in these is testicular in In SHBG in human testis that human Sertoli cells produce SHBG is SHBG in the human testis are in testis in that the of human sequence human SHBG are of a which to under the control of a promoter is in the testis to cells and to of SHBG that in the of a SHBG transgene is expressed in Sertoli cells and in the human SHBG transgene is expressed in but is not expressed in the testis to that the human SHBG promoter in way the promoters in mammals that produce SHBG androgen-binding in Sertoli and a that the human SHBG promoter a potential by which is not in the SHBG promoters of of this footprint 4 (FP4) a human SHBG transgene its expression in Sertoli cells in and the transgene to in a that of the SHBG in Sertoli we have also that the and to FP4 in the human SHBG promoter we that this its in Sertoli mice containing a of the human SHBG gene have characterized FP4 sequence within the SHBG promoter was the human SHBG transgene the in the and was into the by into mice a the A and by of human SHBG transgene under and and of mice the of Sertoli cells cells and by the of the of and of and Sertoli cells and cells the of and mice and Sertoli a of Sertoli and cells was in containing and cells by and of the Sertoli Sertoli cells in this way to in containing cells of and and human SHBG by was and testicular cells was the was by a in the of and to a was a human SHBG and A also as control and the of human SHBG in testicular we also a human as as as was and Sertoli to the of a a human SHBG and a containing the human SHBG in the in of in the was in a of the and by Sertoli as Sertoli in as A to in of in the to of and A to in also as in the a sequence FP4 a FP4 sequence in which the within the was and a sequence the promoter containing a to the and the was to and the of the of and the In and by and the was and to a the and in the Sertoli cells and cells mice and the cells in and cells and in and to to was and 4 of of the control and control in the and to the and 4 the was the in and and to the and 4 and the was was to of of and of the SHBG promoter and to a to in to the and FP4 in the human SHBG promoter a of of and of the promoter was and by in a and of SHBG of human and SHBG promoter in the that a (FP4) in the human SHBG promoter is in the SHBG promoter but is absent in the SHBG promoters of the of the and SHBG promoters this of this a that it a potential in in the human SHBG promoter is to and and the these a by a of are the within the human SHBG these in the and SHBG promoters have and of FP4 Expression of SHBG in Sertoli human SHBG are not in testis mice harboring the human SHBG are in the testis of mice containing the of the human SHBG in which FP4 deleted of the FP4 sequence within this transgene its expression in the liver as by of SHBG SHBG not of mice containing the human SHBG transgene FP4 not of the FP4 the human SHBG promoter in expression of a human SHBG transgene in the testis as as the liver of human SHBG by in the liver of human SHBG mice that the FP4 within the human SHBG human SHBG in the of mice containing the human SHBG transgene in the liver mice and A as and controls of liver and human SHBG by in of a of Sertoli and cells mice containing a human SHBG transgene human SHBG in of a of testicular of the of FP4 within the human SHBG A was to control and to the in a of testicular a was human in the of the of Sertoli and cells mice the human SHBG in which was as which in the testis express the human SHBG testicular cells and a of Sertoli cells and cells by and that human SHBG in of Sertoli cells and cells mice containing the FP4 deleted human SHBG transgene but in of cells these of human SHBG in Sertoli cells of mice that the FP4 deleted transgene that produce and of Sertoli cells the and was SHBG a and that Sertoli cells mice the FP4 deleted human SHBG transgene SHBG and that it in the a human SHBG was in of Sertoli cells mice mice containing the human SHBG transgene SHBG is secreted by Sertoli cells of mice a human SHBG transgene that FP4 within the of of Sertoli cells cells in mice mice containing a human SHBG transgene that the FP4 within the promoter in a of of human SHBG in the a the are SHBG was not in mice containing the human SHBG transgene the of the of androgen-binding by Sertoli we the of SHBG by Sertoli cells mice the FP4 deleted human SHBG transgene In these and human SHBG by these cells A and also SHBG but a testosterone this and and of and testosterone the of human SHBG by Sertoli cells mice containing a human SHBG transgene that FP4 within the of of Sertoli cells cells in mice containing a human SHBG transgene that the FP4 within the promoter in a of of human SHBG in the a the are in SHBG to of and to FP4 within the SHBG in Sertoli in and in Sertoli and as the of and the cells are of the the FP4 are to a which a characterized the the the not a it is not by the of the this is it not to the sequence the is a in the a sequence not the and FP4 as as but not FP4 to the of to the FP4 and in of the in the which was not was and that and FP4 within the human SHBG FP4 and a within the of of the Sertoli in the and and of as was the by was to to and by of and and the of and the FP4 sequence in we a to the human SHBG promoter containing (FP4) as as In these and these are in the testis a control the to the promoter, and was as a control that and the human SHBG promoter mice that the human SHBG transgene of the of the FP4 the and the SHBG promoter mice containing the human SHBG transgene that and FP4 within the human SHBG promoter in to in testicular cells cells and mice containing human SHBG that the FP4 within the promoter and to a and and to the containing and FP4 within the human SHBG a control the in the to the A was in as a control controls of the of the in the in the of as have to the that in SHBG expression in testis of mammals in which Sertoli cells are to androgen-binding into the seminiferous A of SHBG promoter a sequence within the human sequence that is absent in the SHBG promoters of the sequence is in the SHBG promoter and a that we have a by and of liver and the SHBG in and and are expressed the human SHBG in the of we that the of this in SHBG promoters not the of SHBG expression in the of was by the that of the in the of human SHBG transgene not its expression in the liver within the of we have that the human SHBG transgene is not in in the and of the this transgene not this but in the expression of the human SHBG transgene within Sertoli this in of human SHBG of Sertoli cells that express the the way the human SHBG transgene to that of the SHBG gene in Sertoli cells in that and its expression testosterone not have to that the expression of the SHBG gene in Sertoli and the of expression of the human SHBG transgene in of Sertoli cells by was the was of this the of testosterone and the of in Sertoli cells that the FP4 within the human SHBG promoter as a of in Sertoli cells and that this is by the of and as by and and are in Sertoli cells and as In as of but is that of as of a in have that that are in to a within the promoters of the and and this also in the human SHBG promoter where is a In the of the promoter, where and is to expression and it is that FP4 and to the of the human SHBG promoter in Sertoli and are also expressed in the and human SHBG in this is not by the of the of human SHBG in Sertoli cells and to as a in the of these the of that that SHBG gene expression in the human testis is in which androgen-binding within the and a the SHBG promoter is to the human it is that this in the way that the SHBG gene is expressed in the human testis is a that by the human is characterized by seminiferous and this is by and but not it to the SHBG expression in the of that in the human testis in which the human SHBG sequence and this the of the of the of the SHBG in the human testis is in the of the the of the SHBG gene in the human testis. sex hormone-binding globulin (SHBG) SHBG, sex hormone-binding footprint SHBG, sex hormone-binding footprint is produced by and it transports sex steroids in the and to A and as SHBG was in the testis and of and protein, which is to as the testicular androgen-binding protein, to the of the that SHBG A of that androgen-binding by Sertoli cells in is by and but not testosterone this is secreted into the seminiferous and to the where it is by cells it is to to cells within the and of of a in human testis the as SHBG to the that SHBG expression and in the human testis that in human testis are by SHBG, and it to the SHBG in these is testicular in In SHBG in human testis that human Sertoli cells produce SHBG is SHBG in the human testis are in testis in that the of human sequence human SHBG are of a which to under the control of a promoter is in the testis to cells and to of SHBG that in the of In a SHBG transgene is expressed in Sertoli cells and in the human SHBG transgene is expressed in but is not expressed in the testis to that the human SHBG promoter in way the promoters in mammals that produce SHBG androgen-binding in Sertoli and a that the human SHBG promoter a potential by which is not in the SHBG promoters of of this footprint 4 (FP4) a human SHBG transgene its expression in Sertoli cells in and the transgene to in a that of the SHBG in Sertoli we have also that the and to FP4 in the human SHBG promoter we that this its in Sertoli mice containing a of the human SHBG gene have characterized FP4 sequence within the SHBG promoter was the human SHBG transgene the in the and was into the by into mice a the A and by of human SHBG transgene under and and of mice the of Sertoli cells cells and by the of the of and of and Sertoli cells and cells the of and mice and Sertoli a of Sertoli and cells was in containing and cells by and of the Sertoli Sertoli cells in this way to in containing cells of and and human SHBG by was and testicular cells was the was by a in the of and to a was a human SHBG and A also as control and the of human SHBG in testicular we also a human as as as was and Sertoli to the of a a human SHBG and a containing the human SHBG in the in of in the was in a of the and by Sertoli as Sertoli in as A to in of in the to of and A to in also as in the a sequence FP4 a FP4 sequence in which the within the was and a sequence the promoter containing a to the and the was to and the of the of and the In and by and the was and to a the and in the Sertoli cells and cells mice and the cells in and cells and in and to to was and 4 of of the control and control in the and to the and 4 the was the in and and to the and 4 and the was was to of of and of the SHBG promoter and to a to in to the and FP4 in the human SHBG promoter a of of and of the promoter was and by in a and mice containing a of the human SHBG gene have characterized FP4 sequence within the SHBG promoter was the human SHBG transgene the in the and was into the by into mice a the A and by of human SHBG transgene under and and of mice the of Sertoli cells cells and by the of the of and of and Sertoli cells and cells the of and mice and Sertoli a of Sertoli and cells was in containing and cells by and of the Sertoli Sertoli cells in this way to in containing cells of and and human SHBG by was and testicular cells was the was by a in the of and to a was a human SHBG and A also as control and the of human SHBG in testicular we also a human as as as was and Sertoli to the of a a human SHBG and a containing the human SHBG in the in of in the was in a of the and by Sertoli as Sertoli in as A to in of in the to of and A to in also as in the a sequence FP4 a FP4 sequence in which the within the was and a sequence the promoter containing a to the and the was to and the of the of and the In and by and the was and to a the and in the Sertoli cells and cells mice and the cells in and cells and in and to to was and 4 of of the control and control in the and to the and 4 the was the in and and to the and 4 and the was was to of of and of the SHBG promoter and to a to in to the and FP4 in the human SHBG promoter a of of and of the promoter was and by in a and of SHBG of human and SHBG promoter in the that a (FP4) in the human SHBG promoter is in the SHBG promoter but is absent in the SHBG promoters of the of the and SHBG promoters this of this a that it a potential in in the human SHBG promoter is to and and the these a by a of are the within the human SHBG these in the and SHBG promoters have and of FP4 Expression of SHBG in Sertoli human SHBG are not in testis mice harboring the human SHBG are in the testis of mice containing the of the human SHBG in which FP4 deleted of the FP4 sequence within this transgene its expression in the liver as by of SHBG SHBG not of mice containing the human SHBG transgene FP4 not which in the testis express the human SHBG testicular cells and a of Sertoli cells and cells by and that human SHBG in of Sertoli cells and cells mice containing the FP4 deleted human SHBG transgene but in of cells these of human SHBG in Sertoli cells of mice that the FP4 deleted transgene that produce and of Sertoli cells the and was SHBG a and that Sertoli cells mice the FP4 deleted human SHBG transgene SHBG and that it in the a human SHBG was in of Sertoli cells mice mice containing the human SHBG transgene SHBG is secreted by Sertoli cells of mice a human SHBG transgene that FP4 within the of of Sertoli cells cells in mice mice containing a human SHBG transgene that the FP4 within the promoter in a of of human SHBG in the a the are SHBG was not in mice containing the human SHBG transgene the of the of androgen-binding by Sertoli we the of SHBG by Sertoli cells mice the FP4 deleted human SHBG transgene In these and human SHBG by these cells A and also SHBG but a testosterone this and and of and testosterone the of human SHBG by Sertoli cells mice containing a human SHBG transgene that FP4 within the of of Sertoli cells cells in mice containing a human SHBG transgene that the FP4 within the promoter in a of of human SHBG in the a the are in SHBG to of and to FP4 within the SHBG in Sertoli in and in Sertoli and as the of and the cells are of the the FP4 are to a which a characterized the the the not a it is not by the of the this is it not to the sequence the is a in the a sequence not the and FP4 as as but not FP4 to the of to the FP4 and in of the in the which was not was and that and FP4 within the human SHBG FP4 and a within the of of the Sertoli in the and and of as was the by was to to and by of and and the of and the FP4 sequence in we a to the human SHBG promoter containing (FP4) as as In these and these are in the testis a control the to the promoter, and was as a control that and the human SHBG promoter mice that the human SHBG transgene of the of the FP4 the and the SHBG promoter mice containing the human SHBG transgene that and FP4 within the human SHBG promoter in to in testicular cells cells and mice containing human SHBG that the FP4 within the promoter and to a and and to the containing and FP4 within the human SHBG a control the in the to the A was in as a control controls of the of the in the in the of as of SHBG of human and SHBG promoter in the that a (FP4) in the human SHBG promoter is in the SHBG promoter but is absent in the SHBG promoters of the of the and SHBG promoters this of this a that it a potential in in the human SHBG promoter is to and and the these a by a of are the within the human SHBG these in the and SHBG promoters have and of FP4 Expression of SHBG in Sertoli human SHBG are not in testis mice harboring the human SHBG are in the testis of mice containing the of the human SHBG in which FP4 deleted of the FP4 sequence within this transgene its expression in the liver as by of SHBG SHBG not of mice containing the human SHBG transgene FP4 not which in the testis express the human SHBG testicular cells and a of Sertoli cells and cells by and that human SHBG in of Sertoli cells and cells mice containing the FP4 deleted human SHBG transgene but in of cells these of human SHBG in Sertoli cells of mice that the FP4 deleted transgene that produce and of Sertoli cells the and was SHBG a and that Sertoli cells mice the FP4 deleted human SHBG transgene SHBG and that it in the a human SHBG was in of Sertoli cells mice mice containing the human SHBG transgene the of the of androgen-binding by Sertoli we the of SHBG by Sertoli cells mice the FP4 deleted human SHBG transgene In these and human SHBG by these cells A and also SHBG but a testosterone this and and of and to FP4 within the SHBG in Sertoli in and in Sertoli and as the of and the cells are of the the FP4 are to a which a characterized the the the not a it is not by the of the this is it not to the sequence the is a in the a sequence not the and FP4 as as but not FP4 to the of to the FP4 and in of the in the which was not was the FP4 sequence in we a to the human SHBG promoter containing (FP4) as as In these and these are in the testis a control the to the promoter, and was as a control that and the human SHBG promoter mice that the human SHBG transgene of the of the FP4 the and the SHBG promoter mice containing the human SHBG transgene have to the that in SHBG expression in testis of mammals in which Sertoli cells are to androgen-binding into the seminiferous A of SHBG promoter a sequence within the human sequence that is absent in the SHBG promoters of the sequence is in the SHBG promoter and a that we have a by and of liver and the SHBG in and and are expressed the human SHBG in the of we that the of this in SHBG promoters not the of SHBG expression in the of was by the that of the in the of human SHBG transgene not its expression in the liver within the of we have that the human SHBG transgene is not in in the and of the this transgene not this but in the expression of the human SHBG transgene within Sertoli this in of human SHBG of Sertoli cells that express the the way the human SHBG transgene to that of the SHBG gene in Sertoli cells in that and its expression testosterone not have to that the expression of the SHBG gene in Sertoli and the of expression of the human SHBG transgene in of Sertoli cells by was the was of this the of testosterone and the of in Sertoli cells that the FP4 within the human SHBG promoter as a of in Sertoli cells and that this is by the of and as by and and are in Sertoli cells and as In as of but is that of as of a in have that that are in to a within the promoters of the and and this also in the human SHBG promoter where is a In the of the promoter, where and is to expression and it is that FP4 and to the of the human SHBG promoter in Sertoli and are also expressed in the and human SHBG in this is not by the of the of human SHBG in Sertoli cells and to as a in the of these the of that that SHBG gene expression in the human testis is in which androgen-binding within the and a the SHBG promoter is to the human it is that this in the way that the SHBG gene is expressed in the human testis is a that by the human is characterized by seminiferous and this is by and but not it to the SHBG expression in the of that in the human testis in which the human SHBG sequence and this the of the of the of the SHBG in the human testis is in the of the the of the SHBG gene in the human testis. have to the that in SHBG expression in testis of mammals in which Sertoli cells are to androgen-binding into the seminiferous A of SHBG promoter a sequence within the human sequence that is absent in the SHBG promoters of the sequence is in the SHBG promoter and a that we have a by and of liver and the SHBG in and and are expressed the human SHBG in the of we that the of this in SHBG promoters not the of SHBG expression in the of was by the that of the in the of human SHBG transgene not its expression in the liver within the of we have that the human SHBG transgene is not in in the and of the this transgene not this but in the expression of the human SHBG transgene within Sertoli this in of human SHBG of Sertoli cells that express the the way the human SHBG transgene to that of the SHBG gene in Sertoli cells in that and its expression testosterone not have to that the expression of the SHBG gene in Sertoli and the of expression of the human SHBG transgene in of Sertoli cells by was the was of this the of testosterone and the of in Sertoli cells that the FP4 within the human SHBG promoter as a of in Sertoli cells and that this is by the of and as by and and are in Sertoli cells and as In as of but is that of as of a in have that that are in to a within the promoters of the and and this also in the human SHBG promoter where is a In the of the promoter, where and is to expression and it is that FP4 and to the of the human SHBG promoter in Sertoli and are also expressed in the and human SHBG in this is not by the of the of human SHBG in Sertoli cells and to as a in the of these the of that that SHBG gene expression in the human testis is in which androgen-binding within the and a the SHBG promoter is to the human it is that this in the way that the SHBG gene is expressed in the human testis is a that by the human is characterized by seminiferous and this is by and but not it to the SHBG expression in the of that in the human testis in which the human SHBG sequence and this the of the of the of the SHBG in the human testis is in the of the the of the SHBG gene in the human testis. and the mice and and of

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.

Comment cette classification a été obtenuedéplier

Prédiction distillée sur la base complète

Imitation des enseignants

Ni prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.

score de la tête « metaresearch » (Codex)0,000
score de la tête « metaresearch » (Gemma)0,000
Version: codex-gemma-dda1882f352aStatut de validation: machine_predicted_unvalidated
Catégories candidatesaucune
Catégories consensuellesaucune
DomaineSignal candidat: aucune · Signal consensuel: aucune
Devis d'étudeSignal candidat: Expérimental (laboratoire) · Signal consensuel: Expérimental (laboratoire)
GenreSignal candidat: Empirique · Signal consensuel: Empirique
Score de désaccord entre enseignants0,018
Score d'incertitude au seuil0,235

Scores Codex et Gemma par catégorie

CatégorieCodexGemma
Métarecherche0,0000,000
Méta-épidémiologie (sens strict)0,0000,000
Méta-épidémiologie (sens large)0,0000,000
Bibliométrie0,0000,000
Études des sciences et des technologies0,0000,000
Communication savante0,0000,000
Science ouverte0,0000,000
Intégrité de la recherche0,0000,000
Charge utile insuffisante (le modèle a refusé de juger)0,0000,000

Scores machine (provisoires)

Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.

Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.

Tête enseignante Opus0,026
Tête enseignante GPT0,262
Écart entre enseignants0,236 · la distance entre les deux têtes enseignantes sur ce seul travail
Statut de validationscore_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle

Classification

machine, non validée

Prédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.

Les modèles n’ont appliqué aucune catégorie : rien dans la taxonomie ne correspondait à ce travail.
Devis d'étudeExpérimental (laboratoire)
Domainenon disponible
GenreEmpirique

Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».

En bref

Citations34
Publié2004
Routes d'admission1
Résumé présentoui

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Même revueJournal of Biological ChemistryMême sujetSperm and Testicular FunctionTravaux en français237 207