17β-Estradiol Enhances the Production of Nerve Growth Factor in THP-1-Derived Macrophages or Peripheral Blood Monocyte-Derived Macrophages

Abstract

We examined in vitro effects of 17β-estradiol (E2) on nerve growth factor production by macrophages derived from monocytic cell line THP-1-or periphereal blood monocytes. E2 and membrane-impermeable bovine serum albumin-conjugated E2 (E2-BSA) enhanced nerve growth factor secretion and mRNA expression in both types of macrophages E2 enhanced nerve growth factor promotor activity in THP-1-derived macrophages and two activator protein-1 binding sites on the promoter were responsible for the enhancement. E2 and E2-BSA enhanced transcriptional activity and DNA binding of activator protein-1. E2 and E2-BSA shifted the activator protein-1 composition from c-Jun homodimers to c-Fos/c-Jun heterodimers. E2 and E2-BSA transiently induced c-Fos mRNA, which was constitutively undetectable in both types of macrophages. Adenylate cyclase inhibitor SQ22536 suppressed E2-induced nerve growth factor production and c-Fos expression. E2 and E2-BSA increased intracellular cyclic adenosine monophosphate level in both types of macrophages. Antisense oligonucleotide against guanine nucleotide-binding protein-coupled receptor, GPR30 suppressed the E2-induced cyclic adenosine monophosphate signal, c-Fos expression, and nerve growth factor secretion in both types of macrophages. These results suggest that E2 may enhance nerve growth factor production by inducing c-Fos expression via cyclic adenosine monophosphate signal in macrophages. These effects may be mediated via GPR30.