title: GH/STAT5 signaling during the growth period in livers of mice overexpressing GH.
abstract: GH/STAT5 signaling is desensitized in the liver in adult transgenic mice overexpressing GH; however, these animals present greater body size. To assess whether the STAT5 pathway is active during the growth period in the liver in these animals, and how signaling modulators participate in this process, growing transgenic mice and normal siblings were evaluated. STAT5 does not respond to an acute GH-stimulus, but displays higher basal phosphorylation in the livers of growing GH-overexpressing mice. GH receptor and the positive modulators glucocorticoid receptor and HNF1 display greater abundance in transgenic animals, supporting the activity of STAT5. The negative modulators cytokine-induced suppressor and PTP1B are increased in GH-overexpressing mice. The suppressors SOCS2 and SOCS3 exhibit higher mRNA levels in transgenic mice but lower protein content, indicating that they are being actively degraded. Therefore, STAT5 signaling is increased in the liver in GH-transgenic mice during the growth period, with a balance between positive and negative effectors resulting in accelerated but controlled growth.
authors.affiliation: Facultad de Farmacia y BioquímicaInstituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, ArgentinaDepartment of Geriatrics (A.B.)School of Medicine, Southern Illinois University, Springfield, Illinois, USAInstituto de Biología y Medicina Experimental (CONICET)Vuelta de Obligado 2490, Buenos Aires, Argentina.
authors.forename: Carolina S
authors.initials: CS
authors.lastname: Martinez
authors.affiliation: Facultad de Farmacia y BioquímicaInstituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, ArgentinaDepartment of Geriatrics (A.B.)School of Medicine, Southern Illinois University, Springfield, Illinois, USAInstituto de Biología y Medicina Experimental (CONICET)Vuelta de Obligado 2490, Buenos Aires, Argentina.
authors.forename: Verónica G
authors.initials: VG
authors.lastname: Piazza
authors.affiliation: Facultad de Farmacia y BioquímicaInstituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, ArgentinaDepartment of Geriatrics (A.B.)School of Medicine, Southern Illinois University, Springfield, Illinois, USAInstituto de Biología y Medicina Experimental (CONICET)Vuelta de Obligado 2490, Buenos Aires, Argentina.
authors.forename: María E
authors.initials: ME
authors.lastname: Díaz
authors.affiliation: Facultad de Farmacia y BioquímicaInstituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, ArgentinaDepartment of Geriatrics (A.B.)School of Medicine, Southern Illinois University, Springfield, Illinois, USAInstituto de Biología y Medicina Experimental (CONICET)Vuelta de Obligado 2490, Buenos Aires, Argentina.
authors.forename: Ravneet K
authors.initials: RK
authors.lastname: Boparai
authors.affiliation: Facultad de Farmacia y BioquímicaInstituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, ArgentinaDepartment of Geriatrics (A.B.)School of Medicine, Southern Illinois University, Springfield, Illinois, USAInstituto de Biología y Medicina Experimental (CONICET)Vuelta de Obligado 2490, Buenos Aires, Argentina.
authors.forename: Oge
authors.initials: O
authors.lastname: Arum
authors.affiliation: Facultad de Farmacia y BioquímicaInstituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, ArgentinaDepartment of Geriatrics (A.B.)School of Medicine, Southern Illinois University, Springfield, Illinois, USAInstituto de Biología y Medicina Experimental (CONICET)Vuelta de Obligado 2490, Buenos Aires, Argentina.
authors.forename: María C
authors.initials: MC
authors.lastname: Ramírez
authors.affiliation: Facultad de Farmacia y BioquímicaInstituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, ArgentinaDepartment of Geriatrics (A.B.)School of Medicine, Southern Illinois University, Springfield, Illinois, USAInstituto de Biología y Medicina Experimental (CONICET)Vuelta de Obligado 2490, Buenos Aires, Argentina.
authors.forename: Lorena
authors.initials: L
authors.lastname: González
authors.affiliation: Facultad de Farmacia y BioquímicaInstituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, ArgentinaDepartment of Geriatrics (A.B.)School of Medicine, Southern Illinois University, Springfield, Illinois, USAInstituto de Biología y Medicina Experimental (CONICET)Vuelta de Obligado 2490, Buenos Aires, Argentina.
authors.forename: Damasia
authors.initials: D
authors.lastname: Becú-Villalobos
authors.affiliation: Facultad de Farmacia y BioquímicaInstituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, ArgentinaDepartment of Geriatrics (A.B.)School of Medicine, Southern Illinois University, Springfield, Illinois, USAInstituto de Biología y Medicina Experimental (CONICET)Vuelta de Obligado 2490, Buenos Aires, Argentina.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bartke
authors.affiliation: Facultad de Farmacia y BioquímicaInstituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, ArgentinaDepartment of Geriatrics (A.B.)School of Medicine, Southern Illinois University, Springfield, Illinois, USAInstituto de Biología y Medicina Experimental (CONICET)Vuelta de Obligado 2490, Buenos Aires, Argentina.
authors.forename: Daniel
authors.initials: D
authors.lastname: Turyn
authors.affiliation: Facultad de Farmacia y BioquímicaInstituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, ArgentinaDepartment of Geriatrics (A.B.)School of Medicine, Southern Illinois University, Springfield, Illinois, USAInstituto de Biología y Medicina Experimental (CONICET)Vuelta de Obligado 2490, Buenos Aires, Argentina.
authors.forename: Johanna G
authors.initials: JG
authors.lastname: Miquet
authors.affiliation: Facultad de Farmacia y BioquímicaInstituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, ArgentinaDepartment of Geriatrics (A.B.)School of Medicine, Southern Illinois University, Springfield, Illinois, USAInstituto de Biología y Medicina Experimental (CONICET)Vuelta de Obligado 2490, Buenos Aires, Argentina aisotelo@qb.ffyb.uba.ar.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Sotelo
mesh_terms: D000818:Animals; D018507:Gene Expression Regulation, Developmental; D013006:Growth Hormone / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000254:growth & development* / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D011986:Receptors, Somatotropin; D050799:STAT5 Transcription Factor; D050826:Suppressor of Cytokine Signaling Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone
keywords: GH signaling; GH-overexpressing mice; STAT5; growth; liver