17β-Estradiol Promotes Striatal Medium Size Spiny Neuronal Maturation in vitroStroppolo A. · Tian C. · Guinea B. · Olm V. · Sheffield R. · Sommer J. · Ehrlich M.E.
The Nathan Kline Institute, Orangeburg, N.Y., USA
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 17β-estradiol (E2), on the MSN. We report that in vitro, E2 (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 E2, 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 β (ERβ). These data suggest that ERβ may mediate the differentiating effect of E2 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.
Michelle E. Ehrlich, Farber Institute for Neurosciences
Departments of Neurology, Pediatrics, Biochemistry and Molecular Pharmacology
Thomas Jefferson University, 900 Walnut Street JHN4
Philadelphia, PA 19107-5083 (USA)
Tel. +1 215 955 1484, Fax +1 215 503 4358, E-Mail firstname.lastname@example.org
A.S. and C.T. contributed equally to this work.
Received: August 8, 2003
Accepted after revision: April 5, 2004
Published online: June 24, 2004
Number of Print Pages : 9
Number of Figures : 4, Number of Tables : 1, Number of References : 57
Neuroendocrinology (International Journal for Basic and Clinical Studies on Neuroendocrine Relationships)
Founded 1965 by E. Bajusz. Continued by K.M. Knigge (1973–1978), W.F. Ganong (1979–1984), S.M. McCann (1985–1993)
Vol. 79, No. 5, Year 2004 (Cover Date: 2004)
Journal Editor: C. Kordon, Paris
ISSN: 0028–3835 (print), 1423–0194 (Online)
For additional information: http://www.karger.com/journals/nen