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Differential regulation of neuregulin 1 expression by progesterone in astrocytes and neurons

Published online by Cambridge University Press:  26 February 2007

Michael L. Lacroix-Fralish
Affiliation:
Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, USA Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, New Hampshire, USA
Vivianne L. Tawfik
Affiliation:
Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, USA Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, New Hampshire, USA
Nancy Nutile-Mcmenemy
Affiliation:
Anesthesiology and, Dartmouth Medical School, Hanover, New Hampshire, USA Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, New Hampshire, USA
Brent T. Harris
Affiliation:
Pathology, Dartmouth Medical School, Hanover, New Hampshire, USA Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, New Hampshire, USA
Joyce A. Deleo*
Affiliation:
Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, USA Anesthesiology and, Dartmouth Medical School, Hanover, New Hampshire, USA Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, New Hampshire, USA
*
Correspondence should be addressed to Joyce A. Deleo PhD, Departments of Anesthesiology and Pharmacology, HB 7125, One Medical Center Drive, Lebanon, NH 03756, USA email: [email protected]

Abstract

Glial−neuronal interactions are crucial processes in neuromodulation and synaptic plasticity. The neuregulin 1 family of growth and differentiation factors have been implicated as bidirectional signaling molecules that are involved in mediating some of these interactions. We have shown previously that neuregulin 1 expression is regulated by the gonadal hormones progesterone and 17β-estradiol in the CNS, which might represent a novel, indirect mechanism of the neuromodulatory actions of these gonadal hormones. In the present study, we sought to determine the effects of progesterone and 17β-estradiol on neuregulin 1 expression in rat cortical astrocytes and neurons in vitro. We observed that progesterone increased the expression of neuregulin 1 mRNA and protein in a dose-dependent manner in cultured astrocytes, which was blocked by the progesterone receptor antagonist RU-486. In contrast, 17β-estradiol did not increase either neuregulin 1 mRNA or protein in astrocytes. We observed no effect of either progesterone or 17β-estradiol on neuregulin 1 mRNA and protein in rat cortical neurons in vitro. Finally, we observed that treatment of cortical neurons with recombinant NRG1-β1 caused PSD-95 to localize in puncta similar to that observed following treatment with astrocyte-conditioned medium. These results demonstrate that progesterone regulates neuregulin 1 expression, principally in astrocytes. This might represent a novel mechanism of progesterone-mediated modulation of neurotransmission through the regulation of astrocyte-derived neuregulin 1.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2007

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