title: Changes in the content of estrogen alpha and progesterone receptors during differentiation of mouse embryonic stem cells to dopamine neurons.
abstract: Embryonic stem cells (ESC) can differentiate to derivatives of the three embryonic germ layers. Dopamine neurons have been produced from mouse and human ESC. This in vitro induction mimics the developmental program followed by dopaminergic cells in vivo. Production of dopamine neurons might have clinical applications for Parkinson's disease, which has a higher incidence in men than in women, suggesting a protective role for sex hormones, particularly progesterone and estradiol. These hormones exert many of their effects through the interaction with their nuclear receptors. In this study, we used a described 5-stage protocol for dopamine neuron differentiation of ESC, allowing neuronal commitment as evidenced by specific markers and by behavioural recovery of hemiparkinsonian rats after grafting. We studied the expression of steroid hormone receptors by immunoblot during this procedure and found an increase in the content of both A and B isoforms of progesterone receptor (PR) and a decrease in estrogen receptor alpha (ER-alpha) when cells were at the neural/neuronal stages, when compared with the amount found in initial pluripotent conditions. We also found the same pattern of PR and ER-alpha expression by immunocytochemistry. Ninety-two percent of dopamine neurons expressed progesterone receptors and only 19% of these neurons co-expressed tyrosine hydroxylase and ER-alpha. These results show a differential expression pattern of ER-alpha and PR isoforms during neuronal differentiation of ESC.
authors.affiliation: Departamento de Biología, Universidad Nacional Autónoma de México, México, D.F. 04510, Mexico.
authors.forename: Néstor F
authors.initials: NF
authors.lastname: Díaz
authors.forename: Christian
authors.initials: C
authors.lastname: Guerra-Arraiza
authors.forename: Néstor E
authors.initials: NE
authors.lastname: Díaz-Martínez
authors.forename: Patricia
authors.initials: P
authors.lastname: Salazar
authors.forename: Anayansi
authors.initials: A
authors.lastname: Molina-Hernández
authors.forename: Ignacio
authors.initials: I
authors.lastname: Camacho-Arroyo
authors.forename: Ivan
authors.initials: I
authors.lastname: Velasco
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D003720:Densitometry; D004298:Dopamine / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D053595:Embryonic Stem Cells / Q000502:physiology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D016627:Oxidopamine; D011247:Pregnancy; D011980:Receptors, Progesterone / Q000378:metabolism*; D033581:Stem Cell Transplantation; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
chemical_list: D047628:Estrogen Receptor alpha; D009419:Nerve Tissue Proteins; D050814:Octamer Transcription Factor-3; D011980:Receptors, Progesterone; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine