Effects of perfluoroalkyl substances on neurosteroid synthetic enzymes in the rat

- The potencies of perfluoroalkyl substances to inhibit rat SRD5A1, AKR1C9, and RoDH2: PFOS > PFOA > PFHxS = PFBS.
- There are structure-dependent differences for the inhibition.
- PFOS and PFOA with 8 carbons inhibit SRD5A1, AKR1C9, and RoDH2 significantly.
- PFOS and PFOA competitively inhibit rat SRD5A1.

Perfluoroalkylated substances (PFASs), including perfluorooctyl sulphonate (PFOS) and perfluorooctane acid (PFOA), have been classified as persistent organic pollutants and are known to cause endocrine-disrupting effects in humans. The objective of the present study was to compare the potencies of four different PFASs, PFOS, PFOA, perfluorohexyl sulfonate (PFHxS), and perfluorobutyl sulfonate (PFBS), to inhibit neurosteroidogenic 5α-reductase 1 (SRD5A1), 3α-hydroxysteroid dehydrogenase (AKR1C9), and retinol dehydrogenase 2 (RoDH2) in rats. The potencies of PFASs to inhibit SRD5A1 are PFOS > PFOA > PFHxS = PFBS, with IC50 values of PFOS and PFOA of 1.92 ± 0.07 and 14.24 ± 0.07 μM and no effects for PFHxS and PFBS at 100 μM, respectively. The potencies of PFASs to inhibit AKR1C9 and RoDH2 are PFOS > PFOA > PFHxS = PFBS, with IC50 values of PFOS and PFOA on these two enzymes about 100 μM and no effects for PFHxS and PFBS at 100 μM, respectively. PFOS and PFOA competitively inhibited rat SRD5A1. In conclusion, PFOS and PFOA are potent inhibitors of rat SRD5A1, thereby controlling the biosynthesis of neurosteroids.

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