dc.creatorPeinetti, Nahuel
dc.creatorCuello Rubio, Mariana Micaela
dc.creatorSosa, Liliana del Valle
dc.creatorScalerandi, María Victoria
dc.creatorAlasino, Roxana Valeria
dc.creatorPeyret, Victoria
dc.creatorde Nicola, Juan Pablo
dc.creatorBeltramo, Dante Miguel
dc.creatorQuintar, Amado Alfredo
dc.creatorMaldonado, Cristina Alicia
dc.date.accessioned2021-09-15T13:51:15Z
dc.date.accessioned2022-10-15T15:09:12Z
dc.date.available2021-09-15T13:51:15Z
dc.date.available2022-10-15T15:09:12Z
dc.date.created2021-09-15T13:51:15Z
dc.date.issued2020-12
dc.identifierPeinetti, Nahuel; Cuello Rubio, Mariana Micaela; Sosa, Liliana del Valle; Scalerandi, María Victoria; Alasino, Roxana Valeria; et al.; Testosterone-loaded GM1 micelles targeted to the intracellular androgen receptor for the specific induction of genomic androgen signaling; Elsevier Science; International Journal Of Pharmaceutics; 591; 12-2020; 1-11
dc.identifier0378-5173
dc.identifierhttp://hdl.handle.net/11336/140386
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/4400818
dc.description.abstractAndrogens play a central role in homeostatic and pathological processes of the prostate gland. At the cellular level, testosterone activates both the genomic signaling pathway, through the intracellular androgen receptor (AR), and membrane-initiated androgen signaling (MIAS), by plasma membrane receptors. We have previously shown that the activation of MIAS induces uncontrolled proliferation and fails to stimulate the beneficial immunomodulatory effects of testosterone in prostatic cells, becoming necessary to investigate if genomic signaling mediates homeostatic effects of testosterone. However, the lack of specific modulators for genomic androgen signaling has delayed the understanding of this mechanism. In this article, we demonstrate that monosialoganglioside (GM1) micelles are capable of delivering testosterone into the cytoplasm to specifically activate genomic signaling. Stimulation with testosterone-loaded GM1 micelles led to the activation of androgen response element (ARE)-regulated genes in vitro as well as to the recovery of normal prostate size and histology after castration in mice. In addition, these micelles avoided MIAS, as demonstrated by the absence of rapid signaling pathway activation and the inability to induce uncontrolled cell proliferation. In conclusion, our results validate a novel tool for the specific activation of genomic androgen signaling and demonstrate the importance of selective pathway activation in androgen-mediated proliferation.
dc.languageeng
dc.publisherElsevier Science
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1016/j.ijpharm.2020.119985
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0378517320309704
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectANDROGEN RECEPTOR (AR)
dc.subjectGENOMIC ANDROGEN SIGNALING
dc.subjectMEMBRANE-INITIATED ANDROGEN SIGNALING (MIAS)
dc.subjectMONOSIALOGANGLIOSIDE (GM1)
dc.subjectNANOPARTICLES
dc.subjectPROSTATE
dc.subjectTESTOSTERONE
dc.titleTestosterone-loaded GM1 micelles targeted to the intracellular androgen receptor for the specific induction of genomic androgen signaling
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


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