The INHIBITION OF NICOTINAMIDE-ADENINE DINUCLEOTIDE-LINKED 3α-Hydroxy STEROID DEHYDROGENASE BY CERTAIN ANTIMETABOLIC DRUGS

Lambe, R. F.; Williams, D. C.

doi:10.1042/bj0950847

Cited by 8 publications

(1 citation statement)

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“…IC50 value was determined by the method of Chou and Talalay [15], and Kj value by the plots as described by Dixon [16] and Cornish-Bowden [17], ductase activity which catalyzes the reduc tion of various nonsteroidal carbonyl com pounds [9,10] and dihydrodiol dehydroge nase activity [11] which has been suggested to participate in the detoxification of proxi mate diol metabolites of polycyclic hydro carbons [12], The similarity of the two en zymes from rat and guinea pig liver made us test the inhibitory effects of the antiinflam matory agents on guinea pig liver T17ßDH isozymes. Rat liver 3aHSDH has also been reported to be inhibited by 17ß-estradiol and diethylstilbestrol [13], and guinea pig liver T17ßDH by 17ß-estradiol [6]. In this study, we compared the inhibitory effects of antiin flammatory drugs, hydroxysteroids and non steroidal estrogens on the two isozymes of T17ßDH and 3aHSDH.…”

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confidence: 99%

Inhibition of Hepatic 17ß- and 3a-Hydroxysteroid Dehydrogenases by Antiinflammatory Drugs and Nonsteroidal Estrogens

Hasebe¹,

Hara²,

Nakayama³

et al. 1987

Enzyme

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Antiinflammatory agents and estrogens have been tested as inhibitors of two isozymes of guinea pig liver testosterone 17ß-dehydrogenase (NADP) (EC 1.1.1.64) and rat liver 3a-hydroxysteroid dehydrogenase (EC 1.1.1.50). Antiinflammatory steroids and estradiols were highly inhibitory to 3α-hydroxysteroid dehydrogenase and one isozyme of testosterone 17ß-dehydrogenase, respectively, but nonsteroidal antiinflammatory agents and nonsteroidal estrogens such as hexestrol, dienstrol, diethylstilbestrol and zearalenone showed potent inhibitions on all the enzymes. Although the inhibitory potency of indomethacin for one isozymes of testosterone 17ß-dehydrogenase and 3α-hydroxysteroid dehydrogenase decreased with changing pH from 9.7 to 7.0, that of the nonsteroidal estrogens for all the enzymes was little affected by pH. No additive effect in double inhibitor experiments with indomethacin and the nonsteroidal estrogens was observed, and the compounds were all competitive inhibitors with respect to steroidal substrate. The results suggest that there is a very similar region in substrate binding sites of the enzymes.

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