Figure 6.

Proposed signaling pathways implicated in the promoter-specific expression of CYP19 in Hs578t cells. It is proposed that thiacloprid and imidacloprid block the JAK/STAT3 pathway, which regulates I.4 promoter activity via a yet unknown mechanism. In addition, based on the effects of pathway inhibitors, the neonicotinoids are proposed to increase PII/I.3-mediated CYP19 expression in Hs578t cells via stimulation of the PLC pathway. Thiacloprid may also induce I.7-mediated CYP19 expression by stimulation of the MEK/MAPK 1/3 pathway. ${\text{CA}2}^{2+}$, calcium ion; cAMP, cyclic adenosine monophosphate; X, inhibition; ELK, electron transport system transcription factor; GAS, gamma interferon activation site; Imida, imidacloprid; JAK, Janus kinase; lightning bolt, activation/stimulation; MAPK, mitogen-activated protein kinases; ${\text{PGE}}_2$, prostaglandin ${\mathrm{E}}_2$; PLC, phospholipase C; STAT, signal transducer and activator of transcription protein; Thiaclo, thiacloprid; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor.