title: 17beta-Estradiol promotes striatal medium size spiny neuronal maturation in vitro.
abstract: Gender differences exist in the development of the nigrostriatal dopamine system, and in the incidence and course of pediatric and adult neuropsychiatric diseases in which this system is implicated. The medium size spiny neuron (MSN) is the major output neuron of the caudate nucleus. It receives a large dopaminergic input from the substantia nigra, and 96% of the MSNs express DARPP-32, a dopamine and cyclic AMP-regulated phosphoprotein and key mediator of dopamine function. There are few examples, however, of direct effects of sex hormones, including 17beta-estradiol (E(2)), on the MSN. We report that in vitro, E(2) (10-50 nM) promotes MSN phenotypic maturation, as determined by increased soma size, neurite length, and DARPP-32 protein levels. Treatment with the 'anti-estrogen' ICI 182,780 or the partial-agonist tamoxifen also increases DARPP-32 levels, but when added to E(2), ICI 182,780 only prevents the increase in DARPP-32 levels and increase in soma size and neurite length. Surprisingly, maturation effects are more robust in cells derived exclusively from female embryos. Western blot analysis of protein lysates and immunocytochemistry of cultured MSNs reveals the presence of the estrogen receptor beta (ERbeta). These data suggest that ERbeta may mediate the differentiating effect of E(2) on embryonic MSNs, and provide new avenues of investigation for the role of sex hormones in the development of the striatum and in diseases affecting the basal ganglia.
authors.affiliation: The Nathan Kline Institute, Orangeburg, NY, USA.
authors.forename: Antonella
authors.initials: A
authors.lastname: Stroppolo
authors.forename: Chai
authors.initials: C
authors.lastname: Tian
authors.forename: Barbara
authors.initials: B
authors.lastname: Guinea
authors.forename: Vicki
authors.initials: V
authors.lastname: Olm
authors.forename: Roxanne
authors.initials: R
authors.lastname: Sheffield
authors.forename: John
authors.initials: J
authors.lastname: Sommer
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Ehrlich
mesh_terms: D000818:Animals; D002421:Caudate Nucleus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D002478:Cells, Cultured; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D047629:Estrogen Receptor beta; D005260:Female; D000077267:Fulvestrant; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000145:classification / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D012737:Sex Factors; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004965:Estrogen Antagonists; D047629:Estrogen Receptor beta; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D011960:Receptors, Estrogen; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol