17β-Estradiol Primes Elicitation of Inducible Nitric Oxide Synthase Expression by Lipopolysaccharide and Interferon-γ in Mouse Macrophage Cell Line J774.1

The effects of estrogenic compounds on nitric oxide (NO) production by macrophages were examined. 17β-Estradiol promoted NO production triggered by lipopolysaccharide (LPS) and/or interferon (IFN)-γ in the mouse macrophage cell line J774.1. Other estrogen-like substances such as estrone, 17α-ethynylestradiol and bisphenol A also enhanced NO synthesis, but this NO synthesis was not activated by Ca2+ ionophore A23187. RT-PCR analysis demonstrated induction of inducible nitric oxide synthase (iNOS) mRNA in J774.1 cells exposed to 17β-estradiol. Although the estrogen receptor (ER)-antagonist ICI-182780 partially suppressed the promoting effect of 17β-estradiol on NOS activity, there was little ERα detectable by RT-PCR from J774.1 cells. These results suggest that ERs may participate only partially in iNOS mRNA transcription in J774.1 cells and that 17β-estradiol may act directly through other unknown intracellular signal transduction(s) that are activated by LPS and IFN-γ. INTRODUCTION Endocrine hormones play important roles in cell differentiation, growth and the reproductive functions of humans and animals. The endocrine system, immune system and nervous system affect each other, and these three systems organize higher regulation systems to maintain homeostasis in the body 1).