17 -Hydroxysteroid oxidoreductases

The 17P-hydroxysteroid oxidoreductase enzymes (HSOR) occur as two distinct isoforms (I and II). They are involved in the conversion of estrone to estradiol. The type I enzyme converts estrone to estradiol (also androstenedione to testosterone) and the type II catalyses the reverse reaction. Phytoestrogens have been shown to inhibit both HSOR enzymes in vitro. 

Makela S, Poutanen M, Kostlan ML et al. Inhibition of 17 beta-hydroxysteroid oxidoreductase by flavonoids in breast and prostate cancer cells. Proc. Soc. Exp. Biol. Med. 217, 310-316, 1998. 

Warneck, H.M. and Seitz, H.U. (1990) 3b-hydroxysteroid oxidoreductase in suspension cultures of Digitalis lanata EHRH. Z. Naturforsch., 45c, 963-72. 

Metabolism studies. GC-MS is a powerful technique for following and identifying the metabolic products from the in vitro incubation of tissue preparations with steroid substrates. Examples of such studies include the 16a-hydroxylation of 18-hydroxydeoxycorticosterone by human adrenal gland [254], the eiromatization of 3jS,15, 16 -trihydroxy-5-androsten-17-one by placental homogenates [255], and the demonstration of 1/3, 12/3, 6a and 6/3 hydroxylase enzyme activities in microsomal preparations of human foetal hepatic tissue [256]. In the latter study, testosterone was used as substrate and in addition to the hydroxylated metabolites isolated, several other testosterone derivatives indicated the presence of 3a, 3/3 and 17/3-hydroxysteroid oxidoreductase in the adrenal gland preparation. 

After the first demonstration of a direct metabolism of a steroid conjugate [androstenediol sulfate =i dehydroepiandrosterone sulfate (Baulieu et ah, 1963)], showing that a 17j8-hydroxysteroid oxidoreductase can have a sulfo conjugate as a substrate, other enzymic transformations of dehydroepiandrosterone sulfate were reported (Fig. 4). Dehydroepiandrosterone sulfate can undergo 16o -hydroxylation to 16a-hydroxy-dehydroepiandrosterone sulfate which can be further hydroxylated into androstenetriol sulfate its direct 17-hydroxylated metabolite, androstene-... 

Figure 2 Effect of enzyme immobilization on luminescent image spatial resolution evaluated using coupled enzymatic reactions on nylon net as a model system, (a) Immobilized 3a-hydroxysteroid dehydrogenase (b) immobilized 3a-hydroxysteroid dehydrogenase and FMN-NADH oxidoreductase (c) immobilized 3a-hydroxysteroid dehydrogenase, FMN-NADH oxidoreductase, and bacterial luciferase. (From Ref. 47. Copyright John Wiley Sons Ltd. Reproduced with permission.)...

Gibb, W., Jeffery, J. Relationships between the 3 a and 20 [3-hydroxysteroid NAD-oxidoreductase activity of a crystalline-enzyme preparation. European... 

In an early report to a process using three oxidoreductases, namely hydrogenase (ECl.12.2.1), lipoamide dehydrogenase (EC 1.6.4.3) and 20(3-hydroxysteroid dehydrogenase (ECl.1.1.53), a reverse micelle system was used to facilitate stereo- and site-specific reduction of apolar ketosteroids, assisted by the in situ NADH-regenerating enzyme system [61]. 

In 3/i-hydroxysteroid-A5-oxidoreductase deficiency, 7a-hydroxycholesterol undergoes side-chain oxidation, producing 3/l,7a-dihydroxy-5-cholenoic acid and... 

Finsterbusch et al. (1999) discussed that the reactions summarized below may also be catalysed by the Sp-HSD (see Section 6.3.1.2), although they were assigned to putative enzymes, termed 3p-hydroxysteroid 5a-oxidoreductase, 3 3-hydroxysteroid 5p-oxidoreductase and da-hydroxy-steroid 5 3-oxidoreductase. This issue has to be examined further before clear conclusions concerning the role of individual 5-HSOR enzymes in the carde-nolide pathway can be drawn. 

NADPH 3p-hydroxysteroid 5fS-oxidoreductase (3p-HS-5p OR) The 3p-HS-5p-OR catalyses the conversion of 5 3-pregnane-3,20-dione to 5p-pregnane-3p-ol-20-one. It was found to be a soluble protein (Gartner and Seitz, 1993). The reverse reaction was observed, yielding 5 3-pregnane-3,20-dione when using 5(3-pregnane-3(3-ol,20-one and NADP as a substrate and co-substrate, respectively. 

Stuhlemmer, U., Haussmann, W., Milek, R, Kreis, W. and Reinhard, E. (1993a) 3a-Hydroxysteroid-5p-oxidoreductase in tissue cultures of Digitalis lanata. Z. Natur-forsch., 48c, 713-21. 

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