17Beta-estradiol enhances the production of nerve growth factor in THP-1-derived macrophages or peripheral blood monocyte-derived macrophages.
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.
Kanda
Naoko
N
Department of Dermatology, Teikyo University, School of Medicine, Tokyo, Japan. nmk@med.teikyo-u.ac.jp
Watanabe
Shinichi
S
D000328:Adult; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D009000:Monocytes / Q000166:cytology; D020932:Nerve Growth Factor / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000502:physiology; D011485:Protein Binding / Q000276:immunology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016372:RNA, Antisense; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D004958:Estradiol; D020932:Nerve Growth Factor; D000242:Cyclic AMP