Publications

• The mouse 3 beta-hydroxysteroid dehydrogenase multigene family includes two functionally distinct groups of proteins.

  Abbaszade I.G., Clarke T.R., Park C.-H.J., Payne A.H.

  The enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) plays an essential role in the biosynthesis of all steroid hormones. We previously reported the isolation, characterization, and tissue-specific expression of four distinct but highly homologous 3 beta HSD cDNAs (forms I, II, III, and IV) ... >> More

  The enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) plays an essential role in the biosynthesis of all steroid hormones. We previously reported the isolation, characterization, and tissue-specific expression of four distinct but highly homologous 3 beta HSD cDNAs (forms I, II, III, and IV). Enzymatic characterization of three of these isoforms demonstrated that mouse 3 beta HSD I and III function as dehydrogenase/isomerases, but 3 beta HSD IV functions exclusively as a 3-ketosteroid reductase. We now report the isolation and characterization of an additional distinct mouse 3 beta HSD cDNA, 3 beta HSD V, which is expressed in the liver of male mice beginning in late puberty. Similar to 3 beta HSD IV, 3 beta HSD V functions exclusively as a 3-ketosteroid reductase converting an active androgen, dihydrotestosterone (DHT), into an inactive androgen, 5 alpha-androstane-3 beta,17 beta-diol. Expressed 3 beta HSD V, however, exhibits a considerably lower apparent Michaelis-Menten constant (Km) value for DHT than 3 beta HSD IV (0.47 microM vs. 2.2 microM, respectively). The complete predicted amino acid sequence of 3 beta HSD II is also reported. The predicted amino acid sequence of mouse 3 beta HSD V reveals that this new form is more closely related to the 3-ketosteroid reductases, mouse 3 beta HSD IV and rat III (93 and 84% identity, respectively), than to the other rodent isoforms that share less than 75% identity.(ABSTRACT TRUNCATED AT 250 WORDS) << Less

  Mol. Endocrinol. 9:1214-1222(1995) [PubMed] [EuropePMC]

• Expression and characterization of isoforms of 3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase in the hamster.

  Rogerson F.M., Lehoux J.-G., Mason J.I.

  The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase (3 beta-HSD) is essential for the production of all classes of steroid hormones. Multiple isozymes of this enzyme have been demonstrated in the kidney and liver of both the rat and the mouse, although the function of the enzyme i ... >> More

  The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase (3 beta-HSD) is essential for the production of all classes of steroid hormones. Multiple isozymes of this enzyme have been demonstrated in the kidney and liver of both the rat and the mouse, although the function of the enzyme in these tissues is unknown. We have characterized three isozymes of 3 beta-HSD expressed in various tissues of the hamster. Both western and northern blot analyses demonstrated very high levels of 3 beta-HSD in the adrenal, kidney and male liver. Conversely, there were extremely low levels of enzyme expression in the female liver. cDNA libraries prepared from RNA isolated from hamster adrenal, kidney and liver were screened with a full-length cDNA encoding human type 1 3 beta-HSD. Separate cDNAs encoding three isoforms of 3 beta-HSD were isolated from these libraries. To examine the properties of the isoforms, the cDNAs were ligated into expression vectors for over-expression in 293 human fetal kidney cells. The type 1 isoform, isolated from an adrenal cDNA library, was identified as a high-affinity 3 beta-hydroxysteroid dehydrogenase. A separate isoform, designated type 2, was isolated from the kidney, and this was also a high-affinity dehydrogenase/isomerase. Two cDNAs were isolated from the liver, one identical in sequence to type 2 of the kidney, and a distinct cDNA encoding an isoform designated type 3. The type 3 3 beta-HSD possessed no steroid dehydrogenase activity but was found to function as a 3-ketosteroid reductase. Thus male hamster liver expresses a high-affinity 3 beta-HSD (type 2) and a 3-ketosteroid reductase (type 3), whereas the kidney of both sexes express the type 2 3 beta-HSD isoform. These differ from the type 1 3 beta-HSD expressed in the adrenal cortex. << Less

  J. Steroid Biochem. Mol. Biol. 55:481-487(1995) [PubMed] [EuropePMC]

• A novel mouse kidney 3 beta-hydroxysteroid dehydrogenase complementary DNA encodes a 3-ketosteroid reductase instead of a 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase.

  Clarke T.R., Bain P.A., Greco T.L., Payne A.H.

  The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3 beta HSD) is essential for the biosynthesis of all steroid hormones. The enzyme catalyzes the conversion of delta 5-3 beta-hydroxysteroids to delta 4-3-ketosteroids. We report the isolation of a novel mouse 3 beta HSD cDNA ... >> More

  The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3 beta HSD) is essential for the biosynthesis of all steroid hormones. The enzyme catalyzes the conversion of delta 5-3 beta-hydroxysteroids to delta 4-3-ketosteroids. We report the isolation of a novel mouse 3 beta HSD cDNA, 3 beta HSD IV, and describe the tissue-specific expression of its mRNA, the enzyme characteristics of the 3 beta HSD IV protein, and the structural and functional relationships it has to other 3 beta HSD isoforms previously characterized in the mouse and rat. The predicted amino acid sequence of mouse 3 beta HSD IV is 77% and 73% identical to that of mouse 3 beta HSD I and III, respectively. Comparison of the nucleotide and amino acid sequences of the four isoforms characterized to date show that 3 beta HSD IV is more distantly related to I, II, and III than these three forms are to each other. 3 beta HSD IV mRNA is only expressed in mouse kidney. In situ hybridization of mouse kidney indicates that expression is found only in the cortex and appears to be associated with the proximal tubules. Transiently expressed 3 beta HSD IV protein could not convert the delta 5-3 beta-hydroxysteroids, pregnenolone or dehydroepiandrosterone, to their respective delta 4-3-ketosteroids, progesterone or androstenedione, nor did it have the capacity to convert 5 alpha-androstane-3 beta, 17 beta-diol to dihydrotestosterone, characteristic enzymatic activities of expressed mouse 3 beta HSD I and III. 3 beta HSD IV could only catalyze the conversion of dihydrotestosterone to 5 alpha-androstanediol in the presence of the cofactor NADPH. Thus, 3 beta HSD IV is a 3-ketosteroid reductase rather than a 3 beta-hydroxysteroid dehydrogenase/isomerase despite its homology to the other members of the 3 beta HSD family. Mouse 3 beta HSD IV is functionally and structurally most closely related to rat 3 beta HSD III, an isoform expressed predominantly in male rat liver. << Less

  Mol. Endocrinol. 7:1569-1578(1993) [PubMed] [EuropePMC]