RESUMEN
During development and through adulthood, differentiation of diverse cell types is controlled by specific genetic and molecular programs for which transcription factors are master regulators of gene expression. Here, we present an overview of the role of nuclear receptors and their selective pharmacological modulators in oligodendrocytes linage, their role in myelination and remyelination and their potential use as a therapeutic strategy for demyelinating diseases. We discuss several aspects of nuclear receptors including: (1) the biochemistry of nuclear receptors superfamily; (2) their role on stem cells physiology, focusing in differentiation and cell removal; (3) the role of nuclear receptor in the oligodendrocytes cell linage, from oligodendrocyte progenitors cells to mature myelinating cells; and (4) the therapeutics opportunities of nuclear receptors for specific demyelinating diseases.
Asunto(s)
Adrenoleucodistrofia/genética , Enfermedad de Alzheimer/genética , Oligodendroglía/metabolismo , Receptores de Ácido Retinoico/genética , Células Madre/metabolismo , Adrenoleucodistrofia/tratamiento farmacológico , Adrenoleucodistrofia/metabolismo , Adrenoleucodistrofia/patología , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Animales , Factores de Transcripción COUP/agonistas , Factores de Transcripción COUP/genética , Factores de Transcripción COUP/metabolismo , Diferenciación Celular , Linaje de la Célula , Drogas en Investigación/uso terapéutico , Regulación de la Expresión Génica , Humanos , Receptores X del Hígado/agonistas , Receptores X del Hígado/genética , Receptores X del Hígado/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Oligodendroglía/efectos de los fármacos , Oligodendroglía/patología , Receptores Nucleares Huérfanos , Receptores Activados del Proliferador del Peroxisoma/agonistas , Receptores Activados del Proliferador del Peroxisoma/genética , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Receptores Citoplasmáticos y Nucleares/agonistas , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores de Ácido Retinoico/agonistas , Receptores de Ácido Retinoico/metabolismo , Células Madre/efectos de los fármacos , Células Madre/patologíaRESUMEN
OBJECTIVE: To study the effect of peritoneal fluid from women with (PF-E) and without (PF-C) endometriosis on P(450)Arom expression in endometrial cells. DESIGN: Experimental study. SETTING: University research unit. PATIENT(S): Forty women of reproductive age with (n = 22) or without (control; n = 18) endometriosis. INTERVENTION(S): Peritoneal fluid and eutopic endometrial samples were obtained during surgery from women with (n = 13 and 9, respectively) and without (n = 4 and 14, respectively) endometriosis. MAIN OUTCOME MEASURE(S): Expression study for P(450)Arom, steroid factor 1 (SF-1), chicken ovalbumin upstream transcription factor I (COUP-TFI), and COUP-TFII messenger RNA (reverse transcriptase-polymerase chain reacion) and/or protein (immunoblot) in isolated endometrial epithelial cells transfected or not with expression vector containing SF-1, COUP-TFI, or COUP-TFII complementary DNAs. RESULT(S): Basal messenger RNA and/or protein expression of P(450)Arom and SF-1 were augmented in endometriosis, and that of COUP-TF was diminished. In control cells, (Bu)(2)cAMP and PF-E increased P(450)Arom and SF-1 expression (but not COUP-TF expression) in a dose-dependent way, an effect not observed with PF-C, adsorbed PF-E, or 10(-5) M indomethacin. Transfected cells confirmed these results. Any treatments modified the studied molecules in endometriosis cells. CONCLUSION(S): These data indicate that molecules contained in PF-E favor an estrogenic microenvironment, suggesting a role in the etiopathogenesis of endometriosis enabling the survival, maintenance, and growth of endometrial implants in the ectopic locations.