Ketosteroid Isomerase Research Articles

Virilization of the External Genitalia of the Female Rat Fetus by Dehydroepiandrosterone

The effects of maternal administration of DHA (Δ5,3β-hydroxyandrosten-17- one) and its 3-sulfo-conjugated form (DHAS) have been investigated on the development of the external genitalia of the female rat fetus. DHA lowers the weight of maternal adrenals, and increases the weight of maternal ovaries. DHAS produces similar maternal effects, but much lower in degree. DHA causes a striking reduction in fetal weight. This steroid producessome clitoral enlargement, and a slight increase in anourethral distance in proportion to dose.The genital changes in the female are qualitatively and quantitatively similar to those produced by cyanoketone in the experimental model of congenital adrenal hyperplasia due to inhibitionof 3β-hydroxysteroid dehydrogenase and Δ5−4,3- ketosteroid isomerase. DHAS does not affect any of the parameters studied in the fetus. The present findings indicate that the virilization of females having endocrinopathies associated with adefect in the dehydrogenase system can be explained by high ...

Maternal and fetal effects of two inhibitors of 3 beta-hydroxysteroid dehydrogenase and delta 5-4,3-ketosteroid isomerase in the rat.

Congenital adrenal enlargement, hypospadias in male fetuses, slight enlargement of the clitoris and of the anourethral distance in female fetuses, and deficient activity of the 3/3-hydroxysteroid dehydrogenase and Δ5–4,3- ketosteroid isomerase system occur in human congenital adrenal hyperplasia due to a genetic deficiency of these enzymes, and in the experimental model of this disease produced by a C-19 substrate analog (2α-cyano-4,4,17α:-trimethylandrost- 5-en-17β-ol-3-one). The present study was undertaken to determine whether similar biologic and enzymatic defects would be produced by 17β-hydroxy-4,4,17α-trimethylandrost- 5-ene-(2,3d)-isoxazole, an analog with about 10 to 20 times less enzyme affinity, and by 2-hydroxymethylene- androstan-17β-ol-17α-methyl-3-one,an analog with the same kinetic properties and enzyme affinity as the cyano-analog. The isoxazole produces the same anatomic and enzymatic defects in mothers, fetuses and immature females as the cyano-analog. Thus, the effects of the isoxazole...

Purification and properties of 3-beta-hydroxysteroid dehydrogenase and delta-5-3-ketosteroid isomerase from bovine corpora lutea.

Abstract 1. 1. Properties and kinetics of 3β- Hydroxysteroid dehydrogenase and Δ 5 -3- ketosteroid isomerase from the bovine ovary have been examined. The enzymes were purified from the microsomal fraction utilizing sonication, (NH4)2SO4 precipitation, dialysis, and column chromatography. With DPN+ as cofactor, the purified dehydrogenase oxidizes the 3β- hydroxy position of C19 and C20 steroids of the Δ 4 , Δ 5 , and 5α series. It was inactive with 3α-, 11β-, 17β- and 21- hydroxy positions as well as the 3β- position of cholesterol and did not utilize TPN+ as cofactor. 2. 2. With a Δ 5 -3β- hydroxy compound as substrate there was no significant formation of the Δ 4 -3β- hydroxy compound during incubation without nucleotide cofactor. Thus, the reactions leading to Δ 4 -3- ketones appear to be ordered, with oxidation of Δ 5 -3β- hydroxy compounds to Δ 5 -3- ketones preceding isomerization to Δ 4 -3- ketones . 3. 3. Behaviour during purification indicated that failure to obtain complete solubilization is responsible for lack of success in complete separation of dehydrogenase and isomerase activities. However, non-identity of the sites effecting dehydrogenation and isomerization is indicated by variation of activity ratios during purification, different inactivation rates and different pH curves. 4. 4. The presence of a single dehydrogenase site for C19 and C21 substrates and a single isomerase site for C19 and C20 substrate is indicated by the relative constancy in activity ratios during purification, the kinetics of equimolar mixtures, the competitive activation by alternate substrates, and the similarities of inactivation rates.