Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments
| dc.rights.license | open | en_US |
| dc.contributor.author | FERNÁNDEZ-ARJONA, María Del Mar | |
| dc.contributor.author | NAVARRO, Juan Antonio | |
| hal.structure.identifier | Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB] | |
| dc.contributor.author | LÓPEZ-GAMBERO, Antonio Jesús | |
| dc.contributor.author | DE CEGLIA, Marialuisa | |
| dc.contributor.author | RODRÍGUEZ, Miguel | |
| dc.contributor.author | RUBIO, Leticia | |
| dc.contributor.author | RODRÍGUEZ DE FONSECA, Fernando | |
| dc.contributor.author | BARRIOS, Vicente | |
| dc.contributor.author | CHOWEN, Julie A. | |
| dc.contributor.author | ARGENTE, Jesús | |
| dc.contributor.author | RIVERA, Patricia | |
| dc.contributor.author | SUÁREZ, Juan | |
| dc.date.accessioned | 2025-05-31T09:25:48Z | |
| dc.date.available | 2025-05-31T09:25:48Z | |
| dc.date.issued | 2024-04-08 | |
| dc.identifier.issn | 2042-6410 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/206801 | |
| dc.description.abstractEn | Background: Children with pregnancy-associated plasma protein-A2 (PAPP-A2) mutations resulting in low levels of bioactive insulin-like growth factor-1 (IGF1) and progressive postnatal growth retardation have improved growth velocity and height following recombinant human (rh)IGF1 treatment. The present study aimed to evaluate whether Pappa2 deficiency and pharmacological manipulation of GH/IGF1 system are associated with sex-specific differences in growth-related signaling pathways. Methods: Plasma, hypothalamus, pituitary gland and liver of Pappa2ko/ko mice of both sexes, showing reduced skeletal growth, and liver of these mice treated with rhGH, rhIGF1 and rhPAPP-A2 from postnatal day (PND) 5 to PND35 were analyzed. Results: Reduced body and femur length of Pappa2ko/ko mice was associated with increases in: (1) components of IGF1 ternary complexes (IGF1, IGFBP5/Igfbp5, Igfbp3, Igfals) in plasma, hypothalamus and/or liver; and (2) key signaling regulators (phosphorylated PI3K, AKT, mTOR, GSK3β, ERK1/2 and AMPKα) in hypothalamus, pituitary gland and/or liver, with Pappa2ko/ko females having a more prominent effect. Compared to rhGH and rhIGF1, rhPAPP-A2 specifically induced: (1) increased body and femur length, and reduced plasma total IGF1 and IGFBP5 concentrations in Pappa2ko/ko females; and (2) increased Igf1 and Igf1r levels and decreased Ghr, Igfbp3 and Igfals levels in the liver of Pappa2ko/ko females. These changes were accompanied by lower phospho-STAT5, phospho-AKT and phospho-ERK2 levels and higher phospho-AMPK levels in the liver of Pappa2ko/ko females. Conclusions: Sex-specific differences in IGF1 system and signaling pathways are associated with Pappa2 deficiency, pointing to rhPAPP-A2 as a promising drug to alleviate postnatal growth retardation underlying low IGF1 bioavailability in a female-specific manner. © The Author(s) 2024. | |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
| dc.subject.en | Growth | |
| dc.subject.en | Sexual dimorphism | |
| dc.subject.en | Pappalysin-2 | |
| dc.subject.en | IGF1 | |
| dc.subject.en | GH | |
| dc.subject.en | PI3K | |
| dc.subject.en | mTOR | |
| dc.subject.en | AMPK | |
| dc.subject.en | Hypothalamus | |
| dc.subject.en | Pituitary gland | |
| dc.subject.en | Liver | |
| dc.title.en | Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments | |
| dc.title.alternative | Biol Sex Differ | en_US |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1186/s13293-024-00603-5 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC] | en_US |
| dc.identifier.pubmed | 38589872 | en_US |
| dc.description.sponsorshipEurope | European Regional Development Fund | en_US |
| bordeaux.journal | Biology of Sex Differences | en_US |
| bordeaux.page | 34 | en_US |
| bordeaux.volume | 15 | en_US |
| bordeaux.hal.laboratories | Neurocentre Magendie - U1215 | en_US |
| bordeaux.issue | 1 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | INSERM | en_US |
| bordeaux.team | Physiopathologie de l'équilibre énergétique et obésité | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.identifier.funderID | Ministerio de Ciencia e Innovación | en_US |
| bordeaux.identifier.funderID | Ministerio de Economía y Competitividad | en_US |
| bordeaux.identifier.funderID | Instituto de Salud Carlos III | en_US |
| hal.identifier | hal-05091206 | |
| hal.version | 1 | |
| hal.date.transferred | 2025-05-31T09:25:55Z | |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | true | |
| dc.rights.cc | CC BY | en_US |
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