Fig. (2).

Estradiol regulates the expression of tryptophan hydroxylase-2 (TPH-2), monoamine oxidases (MAOs), serotonin transporter (SERT) and serotonin-1A receptor (5-HT1A) through classical mechanisms. Classically, estradiol-activated estrogen receptor dimers contact estrogen response elements (ERE) in the promoter regions of target genes, such as TPH-2, MAO-B and SERT, to initiate transcription. Besides, estrogen receptor can modulate the expression of genes without directly binding to deoxyribonucleic acid by tethering to other transcription factors, including specificity protein 1 (Sp1) and activator protein 1 (AP-1), nuclear factor kappa B (NF-ҡB) and CCAAT/enhancer binding protein β (C/EBPβ). The MAO-A promoter does not contain canonical ERE, however, the presence of three Sp1 sites may provide a mechanism for estradiol regulation. The 5-HT1A gene lacks canonical ERE, but the promoter contains two putative NF-ҡB binding sites that could mediate the estradiol action indirectly through interaction between estrogen receptor and NF-ҡB binding.