Neuron Glia Biology

Research Article

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

Michael L. Lacroix-Fralisha1a4, Vivianne L. Tawfika1a4, Nancy Nutile-Mcmenemya2a4, Brent T. Harrisa3a4 and Joyce A. Deleoa1a2a4 c1

a1 Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, USA

a2 Anesthesiology and, Dartmouth Medical School, Hanover, New Hampshire, USA

a3 Pathology, Dartmouth Medical School, Hanover, New Hampshire, USA

a4 Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, New Hampshire, USA

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.

(Received October 26 2006)

(Revised November 27 2006)

(Accepted November 28 2006)

Correspondence:

c1 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: Joyce.A.DeLeo@Dartmouth.edu