Estradiol synthesis pathways are upregulated in human CRC. (A) Estrogen metabolism pathways demonstrating the importance of STS and HSD17Bs in estrogen synthesis. (B) STS activity is increased in female (n = 29) and male (n = 31) CRC compared with matched normal colon tissue. *P < 0.05, **P < 0.01, ***P < 0.001 using random effects linear regression modeling. (C) STS activity does not correlate with STS expression (dCT) in CRC or normal colon tissue (n = 62). (D) HSD17B2 (female, n = 19; male, n = 28) expression is downregulated in CRC. *P < 0.05, **P < 0.01, ***P < 0.001 (two-tailed paired Student t test used). (E and F) HSD17B7 (female, n = 21; male, n = 22) and HSD17B12 (female, n = 21; male, n = 22) expression is upregulated in CRC. *P < 0.05, **P < 0.01, ***P < 0.001 (two-tailed paired Student t test used). (G and H) Representative blots and relative intensity (arbitrary unit) of HSD17B enzymes in normal and matched cancerous human colon tissue. HSD17B1 (n = 16) protein expression was not present in human CRC, but HSD17B7 was expressed, and HSD17B12 expression was increased (n = 16), with little change in HSD17B2 expression (n = 16). For relative intensity data, a two-tailed Student t test was used. All data presented as mean ± standard deviation.