The dual sex hormone specificity for human reductive 17β-hydroxysteroid dehydrogenase type 7: Synergistic function in estrogen and androgen control

The Journal of Steroid Biochemistry and Molecular Biology
Jean-François Thériault, Sheng-Xiang Lin

Abstract

Human 17β-hydroxysteroid dehydrogenase (17β-HSD) type 1 and 7 catalyze the final step of estrogen activation and the first step in androgen inactivation. It has been shown in breast cancer cells that DHT has a suppression effect on cell proliferation, counteracting the estrogen growth effect. However, the exact kinetic function of 17β-HSD7 in steroidogenesis was not determined. Here we report the steady-state kinetics and binding study for 17β-HSD7 with estrone or DHT as substrates and NADPH as cofactor. 17β-HSD7 has been overexpressed in E. coli and purified. For both substrates, kinetics of 17β-HSD7 demonstrates positive cooperativity. The K0.5 value is 5.2 ± 0.4 μM and 14.4 ± 0.8 μM and the kcat is 0.0063 ± 0.0003 s-1 and 0.0153 ± 0.0007 s-1 for the reduction of E1 and DHT, respectively. The binding study shows a similar affinity with a dissociation constant of 5.2 ± 0.5 μM and 11 ± 1 μM for E1 and DHT, respectively. Our kinetic and binding results reveal a positive cooperativity for 17β-HSD7 to both the E1 and DHT with a similar affinity, while 17β-HSD1 demonstrated a significantly higher affinity toward E1 than DHT, but with a strong E1 substrate inhibition. These results strongly support that the inhibition of 17β-HSD7 co...Continue Reading

Citations

Oct 15, 2019·The Journal of Steroid Biochemistry and Molecular Biology·Tang LiSheng-Xiang Lin
Aug 18, 2021·The Journal of Steroid Biochemistry and Molecular Biology·Jean-Francois ThériaultSheng-Xiang Lin

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