17Beta-estradiol enhances the production of nerve growth factor in THP-1-derived macrophages or peripheral blood monocyte-derived macrophages

J Invest Dermatol. 2003 Oct;121(4):771-80. doi: 10.1046/j.1523-1747.2003.12487.x.


We examined in vitro effects of 17beta-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Line
  • Cyclic AMP / metabolism
  • Estradiol / pharmacology*
  • Humans
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / physiology*
  • Monocytes / cytology
  • Nerve Growth Factor / genetics*
  • Promoter Regions, Genetic / physiology
  • Protein Binding / immunology
  • Proto-Oncogene Proteins c-fos / metabolism
  • Proto-Oncogene Proteins c-jun / metabolism
  • RNA, Antisense
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Transcription Factor AP-1 / metabolism
  • Transcription, Genetic / physiology


  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • RNA, Antisense
  • RNA, Messenger
  • Transcription Factor AP-1
  • Estradiol
  • Nerve Growth Factor
  • Cyclic AMP