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Gene Review

HSD3B1  -  hydroxy-delta-5-steroid dehydrogenase, 3...

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Disease relevance of HSD3B


High impact information on HSD3B

  • The 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta HSD) enzyme catalyzes the oxidation and isomerization of delta 5-3 beta-hydroxysteroid precursors into delta 4-ketosteroids, thus leading to the formation of all classes of steroid hormones [2].
  • The present data show for the first time that adrenals and gonads express a type of 3 beta HSD isoenzyme that is distinct from the type expressed in the placenta.(ABSTRACT TRUNCATED AT 400 WORDS)[2]
  • Moreover, incubation in the presence of NADH of homogenates from cells transfected with type I or type II 3 beta HSD indicates that dihydrotestosterone is converted into 5 alpha-androstane-3 beta, 17 beta-diol, with Km values of 0.26 and 2.7 microM, respectively [2].
  • To characterize and compare the kinetic properties of the two isoenzymes, plasmids derived from pCMV and containing type I or type II 3 beta HSD full-length cDNA inserts were transiently expressed in HeLa human cervical carcinoma cells [2].
  • Such intermembrane fusion sites would facilitate the access of cholesterol to the inner membrane in which cholesterol side-chain cleavage cytochrome P-450 is located as well as the rapid transformation of its reaction product (i.e. pregnenolone) to progesterone by 3 beta HSD/I [3].

Biological context of HSD3B

  • We have used our recently characterized human 3 beta-hydroxy-5-ene steroid dehydrogenase/delta 5-delta 4-isomerase (3 beta-HSD) cDNA as probe to isolate cDNAs encoding bovine 3 beta-HSD from a bovine ovary lambda gtll cDNA library [4].
  • The deduced amino acid sequence of bovine 3 beta-HSD displays 79% homology with human 3 beta-HSD while the nucleotide sequence of the coding region shares 82% interspecies similarity [4].
  • The results suggest that mitochondrial 3 beta HSD is an integral inner membrane protein, that the active site faces the matrix space and is influenced by coenzyme availability, and that a regulatory site(s) faces the intermembrane space [5].
  • The levels of 3 beta HSD were extremely low in placental tissues, but were higher in the fetal adrenals, where they were found to be slightly elevated in early and late gestation compared to those in midgestational stages [6].
  • 3 beta HSD mRNA levels in granulosa cells were 4.2-fold higher in early vs. late follicular phase (P < 0.01) [7].

Anatomical context of HSD3B

  • Examination of submitochondrial preparations revealed that 3 beta HSD/I was associated with both the inner membrane and a particulate fraction that sediments in a density gradient between inner and outer membranes [3].
  • In these experiments we examined the membrane topologies of 3 beta HSD in rat and calf adrenal microsomes and mitochondria by comparing access to the active sites of coenzyme and the inhibitor mersalyl, a nonpenetrant organic mercurial anion [5].
  • After 72 h of culture, the signal for P450scc and 3 beta HSD mRNA in granulosa cells exposed to LH was higher than the signal detected in cultures without LH (P < 0.01) [7].
  • Immunocytochemical examination of the levels of P45017 alpha and 3 beta HSD in the fetal adrenal glands correlated with the results of Western and Northern analyses [6].
  • However, because the different stabilities of 3 beta HSD and hydroxylase proteins and/or mRNAs may play a critical role in determining the zone-specific steroids secreted from the adrenal cortex, other cAMP-dependent or independent regulatory mechanisms may also be important in regulating the expression of adrenal 3 beta HSD [8].

Associations of HSD3B with chemical compounds

  • Our objective was to determine whether changes in progesterone production by the preovulatory follicle are effected via changes in mRNA levels for the steroidogenic enzymes cholesterol side-chain cleavage cytochrome P450 (P450scc) and 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3 beta HSD) [7].
  • The content of 3 beta-HSD protein was measured by immunoblot analysis using an antiserum developed in rabbits against human 3 beta-HSD, whereas 3 beta-HSD activity was measured using [3H]pregnenolone, [3H] dehydroepiandrosterone, and [3H]androst-5-ene-3 beta,17 beta-diol as substrates [9].
  • In contrast, mitochondrial 3 beta HSD used matrix space NAD+, was inhibited by reduction of intramitochondrial NAD(P)+, and was insensitive to mersalyl [5].
  • Mitochondrial 3 beta HSD activity may be enhanced by oxidation of intermembrane space NADH via an active rotenone- and antimycin-a-insensitive NADH oxidase [5].
  • 3 beta-HSD was not induced by cyclic AMP or TPA alone, but was induced by the combination of the two agents [10].

Other interactions of HSD3B


Analytical, diagnostic and therapeutic context of HSD3B


  1. Structure-function relationships of 3 beta-hydroxysteroid dehydrogenase: contribution made by the molecular genetics of 3 beta-hydroxysteroid dehydrogenase deficiency. Morel, Y., Mébarki, F., Rhéaume, E., Sanchez, R., Forest, M.G., Simard, J. Steroids (1997) [Pubmed]
  2. Structure and expression of a new complementary DNA encoding the almost exclusive 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase in human adrenals and gonads. Rhéaume, E., Lachance, Y., Zhao, H.F., Breton, N., Dumont, M., de Launoit, Y., Trudel, C., Luu-The, V., Simard, J., Labrie, F. Mol. Endocrinol. (1991) [Pubmed]
  3. Characterization of the 3 beta-hydroxysteroid dehydrogenase activity associated with bovine adrenocortical mitochondria. Cherradi, N., Defaye, G., Chambaz, E.M. Endocrinology (1994) [Pubmed]
  4. Molecular cloning, cDNA structure and predicted amino acid sequence of bovine 3 beta-hydroxy-5-ene steroid dehydrogenase/delta 5-delta 4 isomerase. Zhao, H.F., Simard, J., Labrie, C., Breton, N., Rhéaume, E., Luu-The, V., Labrie, F. FEBS Lett. (1989) [Pubmed]
  5. Topology of 3 beta-hydroxy-5-ene-steroid dehydrogenase/delta 5-delta 4-isomerase in adrenal cortex mitochondria and microsomes. Sauer, L.A., Chapman, J.C., Dauchy, R.T. Endocrinology (1994) [Pubmed]
  6. Expression of steroidogenic enzymes in the bovine placenta and fetal adrenal glands throughout gestation. Conley, A.J., Head, J.R., Stirling, D.T., Mason, J.I. Endocrinology (1992) [Pubmed]
  7. Levels of messenger ribonucleic acid for cholesterol side-chain cleavage cytochrome P-450 and 3 beta-hydroxysteroid dehydrogenase in bovine preovulatory follicles decrease after the luteinizing hormone surge. Voss, A.K., Fortune, J.E. Endocrinology (1993) [Pubmed]
  8. Regulation of 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase expression by adrenocorticotropin in bovine adrenocortical cells. Naville, D., Rainey, W.E., Milewich, L., Mason, J.I. Endocrinology (1991) [Pubmed]
  9. Changes in 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase messenger ribonucleic acid, activity and protein levels during the estrous cycle in the bovine ovary. Couët, J., Martel, C., Dupont, E., Luu-The, V., Sirard, M.A., Zhao, H.F., Pelletier, G., Labrie, F. Endocrinology (1990) [Pubmed]
  10. Expression of 17 alpha-hydroxylase and 3 beta-hydroxysteroid dehydrogenase in fetal human adrenocortical cells transfected with SV40 T antigen. Cheng, C.Y., Flasch, M.V., Hornsby, P.J. J. Mol. Endocrinol. (1992) [Pubmed]
  11. Epitopic heterogeneity of human 3 beta-hydroxysteroid dehydrogenase in villous and extravillous human trophoblast. Hawes, C.S., McBride, M.W., Petropoulos, A., Mueller, U.W., Sutcliffe, R.G. J. Mol. Endocrinol. (1994) [Pubmed]
  12. Changes in levels of messenger ribonucleic acid for cytochrome P450 side-chain cleavage and 3 beta-hydroxysteroid dehydrogenase during prostaglandin F2 alpha-induced luteolysis in cattle. Tian, X.C., Berndtson, A.K., Fortune, J.E. Biol. Reprod. (1994) [Pubmed]
  13. Characteristics of bovine luteal cells in culture: morphology, proliferation and progesterone secretion in different media and effects of LH, dibutyryl cyclic AMP, antioxidants and insulin. O'Shaughnessy, P.J., Wathes, D.C. J. Endocrinol. (1985) [Pubmed]
  14. Expression of 3 beta-hydroxysteroid dehydrogenase in early bovine embryo development. Chiappe, M.E., Lattanzi, M.L., Colman-Lerner, A.A., Barañao, J.L., Saragüeta, P. Mol. Reprod. Dev. (2002) [Pubmed]
  15. Differential effects of oxytocin on steroid production by bovine granulosa cells. Berndtson, A.K., Weaver, C.J., Fortune, J.E. Mol. Cell. Endocrinol. (1996) [Pubmed]
  16. Growth hormone transgenes regulate the expression of sex-specific isoforms of 3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase in mouse liver and gonads. Keeney, D.S., Murry, B.A., Bartke, A., Wagner, T.E., Mason, J.I. Endocrinology (1993) [Pubmed]
  17. Immunohistochemical localization of 3 beta-hydroxysteroid dehydrogenase and P450 17 alpha-hydroxylase during follicular and luteal development in pigs, sheep, and cows. Conley, A.J., Kaminski, M.A., Dubowsky, S.A., Jablonka-Shariff, A., Redmer, D.A., Reynolds, L.P. Biol. Reprod. (1995) [Pubmed]
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