Research Article

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

Michael L. Lacroix-Fralish^a1a4, Vivianne L. Tawfik^a1a4, Nancy Nutile-Mcmenemy^a2a4, Brent T. Harris^a3a4 and Joyce A. Deleo^a1a2a4 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)

KEY WORDS

• Sex hormones;
• neuregulin;
• glial activation;
• PSD-95;
• NGR1

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