TY - JOUR
T1 - Substrate specificity and inhibitor sensitivity of rabbit 20a-hydroxysteroid dehydrogenase
AU - Endo, Satoshi
AU - Arai, Yuki
AU - Hara, Akira
AU - Kitade, Yukio
AU - Bunai, Yasuo
AU - El-Kabbani, Ossama
AU - Matsunaga, Toshiyuki
PY - 2013
Y1 - 2013
N2 - In this study, we examined the substrate specificity and inhibitor sensitivity of rabbit 20a-hydroxysteroid dehydrogenase (AKR1C5), which plays a role in the termination of pregnancy by progesterone inactivation. AKR1C5 moderately reduced the 3-keto group of only 5a-dihydrosteroids with 17?- or 20a/?-hydroxy group among 3-ketosteroids. In contrast, the enzyme reversibly and efficiently catalyzed the reduction of various 17- and 20-ketosteroids, including estrogen precursors (dehydroepiandrosterone, estrone and 5a-androstan-3?- ol-17-one) and tocolytic 5?-pregnane-3,20- dione. In addition to the progesterone inactivation, the formation of estrogens and metabolism of the tocolytic steroid by AKR1C5 may be related to its role in rabbit parturition. AKR1C5 also reduced various non-steroidal carbonyl compounds, including isatin, an antagonist of the C-type natriuretic peptide receptor, and 4-oxo-2-nonenal, suggesting its roles in controlling the bioactive isatin and detoxification of cytotoxic aldehydes. AKR1C5 was potently and competitively inhibited by flavonoids such as kaempferol and quercetin, suggesting that its activity is affected by ingested flavonoids.
AB - In this study, we examined the substrate specificity and inhibitor sensitivity of rabbit 20a-hydroxysteroid dehydrogenase (AKR1C5), which plays a role in the termination of pregnancy by progesterone inactivation. AKR1C5 moderately reduced the 3-keto group of only 5a-dihydrosteroids with 17?- or 20a/?-hydroxy group among 3-ketosteroids. In contrast, the enzyme reversibly and efficiently catalyzed the reduction of various 17- and 20-ketosteroids, including estrogen precursors (dehydroepiandrosterone, estrone and 5a-androstan-3?- ol-17-one) and tocolytic 5?-pregnane-3,20- dione. In addition to the progesterone inactivation, the formation of estrogens and metabolism of the tocolytic steroid by AKR1C5 may be related to its role in rabbit parturition. AKR1C5 also reduced various non-steroidal carbonyl compounds, including isatin, an antagonist of the C-type natriuretic peptide receptor, and 4-oxo-2-nonenal, suggesting its roles in controlling the bioactive isatin and detoxification of cytotoxic aldehydes. AKR1C5 was potently and competitively inhibited by flavonoids such as kaempferol and quercetin, suggesting that its activity is affected by ingested flavonoids.
UR - https://www.jstage.jst.go.jp/article/bpb/36/9/36_b13-00342/_article
U2 - 10.1248/bpb.b13-00342
DO - 10.1248/bpb.b13-00342
M3 - Article
VL - 36
SP - 1514
EP - 1518
JO - Biological & Pharmaceutical Bulletin
JF - Biological & Pharmaceutical Bulletin
SN - 0918-6158
IS - 9
ER -