Skip to main content
SpringerLink
Log in

The 3β-Hydroxysteroid Dehydrogenase/Isomerase Gene Family: Lessons from Type II 3β-HSD Congenital Deficiency

  • Conference paper
Signal Transduction in Testicular Cells

Part of the book series: Ernst Schering Research Foundation Workshop ((SCHERING FOUND,volume 2/1996))

Abstract

The membrane-bound nicotinamide adenine dinucleotide (NAD+)-dependent 3β-hydroxysteroid dehydrogenase /Δ5-Δ4-isomerase (3β-HSD), located in the endoplasmic reticulum and in mitochondrial membrane (Chapman et al. 1992; Cherradi et al. 1993, 1994; Luu-The et al. 1989, 1990; Sauer et al. 1994; Simard et al. 1991a; Thomas et al. 1989), catalyzes the conversion of Δ5-3β-hydroxy steroids into the corresponding Δ4-3-ketosteroids (Fig. 1). This activity is essential for the formation of all classes of steroids, namely, progesterone, mineralocorticoids, glucocorticoids, androgens, and estrogens. In addition, the enzymes of the 3β-HSD family also catalyze the formation and/or degradation of the 5α-androstanes and 5α-pregnanes, such as dihydrotestosterone (DHT) and dihydroprogesterone (Fig. 1) (de Launoit et al. 1992a, b; Labrie et al. 1994b; Luu-The et al. 1989; Mason 1993; Rheaume et al. 1991; Sanchez et al. 1994a; Simard et al. 1991a, 1993a, b; Zhao et al. 1991).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  • Abbaszade I, Clarke T, Park C-H, Payne AH (1995a) The mouse 3β-hydroxysteroid dehydrogenase multigene family includes two functionally distinct groups of proteins. Mol Endocrinol 9:1214–1222.

    Article  PubMed  CAS  Google Scholar 

  • Abbaszade L, Arensburg Y, Clarke T, Kasa-Vubu J, Orly J, Payne AH (1995b) Isolation of mouse 3β-HSD isoform that may be critical for maintenance of early pregnancy. Proceedings of the 77th annual meeting of the Endocrinological Society, abstract 619 P3-601.

    Google Scholar 

  • August GP, Grumbach MM, Kaplan SL (1972) Hormonal changes in puberty. III. Correlation of plasma testosterone, LH, FSH, testicular size, and bone age with male pubertal development. J Clin Endocrinol Metab 34:319–326.

    Article  PubMed  CAS  Google Scholar 

  • Baillie AH, Niemi M, Ikanen M (1965) 3β-hydroxysteroid dehydrogenase activity in the human foetal testis. Acta Endocrinol (Copenh) 48:429–438.

    CAS  Google Scholar 

  • Bain PA, Yoo M, Clarke T, Hammond SH, Payne AH (1991) Multiple forms of mouse 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase and differential expression in gonads, adrenal glands, liver, and kidneys of both sexes. Proc Natl Acad Sci USA 88:8870–8874.

    Article  PubMed  CAS  Google Scholar 

  • Bain PA, Meisler MH, Taylor BA, Payne AH (1993) The genes encoding gonadal and nongonadal forms of 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase are closely linked on mouse chromosome 3. Genomics 16:219–223.

    Article  PubMed  CAS  Google Scholar 

  • Baker ME, Blasco R (1992) Expansion of the mammalian 3β-hydroxysteroid dehydrogenase/plant dihydroflavonol reductase superfamily to include a bacterial cholesterol dehydrogenase, a bacterial UDP-galactose-4-epimerase and open reading frames in vaccinia virus and fish lymphocystis disease virus. FEBS Lett 301:89–93.

    Article  PubMed  CAS  Google Scholar 

  • Baker ME, Luu TY, Simard J, Labrie F (1990) A common ancestor for mammalian 3β-hydroxysteroid dehydrogenase and plant dihydroflavonol reductase (letter). Biochem J 269:558–559.

    PubMed  CAS  Google Scholar 

  • Bérubé D, Luu-The V, Lachance Y, Gagné R, Labrie F (1989) Assignment of the human 3β-hydroxysteroid dehydrogenase gene (HSDB3) to the p13 band of chromosome 1. Cytogenet Cell Genet 52:199–200.

    Article  PubMed  Google Scholar 

  • Bidlingmainer F, Dorr HG, Eisenmenger W, Kuhnle U, Knorr D (1983) Testosterone and androstenedione concentrations in human testis and epididymis during first two years of life. J Clin Endocrinol Metab 57:311–315.

    Article  Google Scholar 

  • Bongiovanni A (1962) The adrenogenital syndrome with deficiency of 3β-hy-droxysteroid dehydrogenase. J Clin Invest 41:2086–2092.

    Article  PubMed  CAS  Google Scholar 

  • Bongiovanni AM (1981) Acquired adrenal hyperplasia: with special reference to 3β-hydroxysteroid dehydrogenase. Fertil Steril 35:599–608.

    PubMed  CAS  Google Scholar 

  • Cara JF, Moshang TJ, Bongiovanni AM, Marx BS (1985) Elevated 17-hydroxyprogesterone and testosterone in a newborn with 3-β-hydroxysteroid dehydrogenase deficiency. N Engl J Med 313:618–621.

    Article  PubMed  CAS  Google Scholar 

  • Chapman JC, Waterhouse TB, Michael SD (1992) Changes in mitochondrial and microsomal 3β-hydroxysteroid dehydrogenase activity in mouse ovary over the course of the estrous cycle. Biol Reprod 47:992–997.

    Article  PubMed  CAS  Google Scholar 

  • Cherradi N, Defaye G, Chambaz EM (1993) Dual subcellular localization of the 3β-hydroxysteroid dehydrogenase isomerase: characterization of the mitochondrial enzyme in the bovine adrenal cortex. J Steroid Biochem Mol Biol 46:773–779.

    Article  PubMed  CAS  Google Scholar 

  • Cherradi N, Defaye G, Chambaz EM (1994) Characterization of the 3β-hydroxysteroid dehydrogenase activity associated with bovine adrenocortical mitochondria. Endocrinology 134:1358–1364.

    Article  PubMed  CAS  Google Scholar 

  • Clarke TR, Bain PA, Greco TL, Payne AH (1993a) A novel mouse kidney β-hydroxysteroid dehydrogenase complementary DNA encodes a 3-ketoste-roid reductase instead of a 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase. Mol Endocrinol 7:1569–1578.

    Article  PubMed  CAS  Google Scholar 

  • Clarke TR, Bain PA, Sha LL, Payne AH (1993b) Enzyme characteristics of 2 distinct forms of mouse 3-β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase complementary deoxyribonucleic acids expressed in COS-1 cells. Endocrinology 132:1971–1976.

    Article  PubMed  CAS  Google Scholar 

  • Dalla Valle L, Couet J, Labrie Y, Simard J, Belvedere P, Simontacchi C, Labrie F, Colombo L (1995) Occurrence of cytochrome P450c17 mRNA and dehydroepiandrosterone biosynthesis in the rat gastrointestinal tract. Mol Cell Endocrinol 111:83–92.

    Article  PubMed  CAS  Google Scholar 

  • de Galarreta CMR, Fanju LF, Meidan R, Hsueh A (1983) Regulation of 3β-hydroxysteroid dehydrogenase activity by human chorionic gonadotropin androgens and anti-androgens in cultures testicular cells. J Biol Chem 258:10988–10996.

    Google Scholar 

  • de Launoit Y, Simard J, Durocher F, Labrie F (1992a) Androgenic 17 β-hy-droxysteroid dehydrogenase activity of expressed rat type I 3β-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase. Endocrinology 130:553–555.

    Article  PubMed  Google Scholar 

  • de Launoit Y, Zhao HF, Bélanger A, Labrie F, Simard J (1992b) Expression of liver-specific member of the 3β-hydroxysteroid dehydrogenase family an isoform possessing an almost exclusive 3-ketosteroid reductase activity. J Biol Chem 267:4513–4517.

    PubMed  Google Scholar 

  • de Peretti E, Forest MG, Feit JP, David M (1980) Endocrine studies in two chidren with male pseudohermaphroditism due to 3β-hydroxysteroid (3β-HSD) dehydrogenase defect. In: Genazzani AR, Thijssen JHH, Siiteri PK (eds) Adrenal androgens. Raven, New York, pp 141–145.

    Google Scholar 

  • Doody KM, Carr BR, Rainey WE, Byrd W, Murry BA, Strickler RC, Thomas JL, Mason JI (1990) 3β-hydroxysteroid dehydrogenase/isomerase in the fetal zone and neocortex of the human fetal adrenal gland. Endocrinology 126:2487–2492.

    Article  PubMed  CAS  Google Scholar 

  • Dumont M, Van LT, Dupont E, Pelletier G, Labrie F (1992) Characterization, expression, and immunohistochemical localization of 3β-hydroxysteroid dehydrogenase/Δ-Δ4 isomerase in human skin. J Invest Dermatol 99:415–421.

    Article  PubMed  CAS  Google Scholar 

  • Dupont E, Luu-The V, Labrie F, Pelletier G (1990a) Ontogeny of 3β-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3β-HSD) in human adrenal gland performed by immunocytochemistry. Mol Cell Endocrinol 74:R7–10.

    Article  PubMed  CAS  Google Scholar 

  • Dupont E, Zhao HF, Rheaume E, Simard J, Luu TV, Labrie F, Pelletier G (1990b) Localization of 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase in rat gonads and adrenal glands by immunocytochemistry and in situ hybridization. Endocrinology 127:1394–1403.

    Article  PubMed  CAS  Google Scholar 

  • Dupont E, Luu TV, Labrie F, Pelletier G (1991) Ontogeny of 3β-hydroxysteroid dehydrogenase/Δ-Δ4 isomerase (3β-HSD) in human testis as studied by immunocytochemistry. J Androl 12:161–164.

    PubMed  CAS  Google Scholar 

  • Dupont E, Labrie F, Luu TV, Pelletier G (1992) Immunocytochemical localization of 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase in human ovary. J Clin Endocrinol Metab 74:994–998.

    Article  PubMed  CAS  Google Scholar 

  • Dupont E, Labrie F, Luu TV, Pelletier G (1993) Ontogeny of 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD) in rat testis as studied by immunocytochemistry. Anat Embryol (Berl) 187:583–589.

    Article  CAS  Google Scholar 

  • Dupont E, Simard J, Luu TV, Labrie F, Pelletier G (1994) Localization of 3 β-hydroxysteroid dehydrogenase in rat brain as studied by in situ hybridization. Mol Cell Neurosci 5:119–23.

    Article  PubMed  CAS  Google Scholar 

  • Durocher F, Sanchez R, Laudet V, Labrie Y, Samson C, Tremblay Y, Labrie F, Simard J (1994) Structural and functional characterization of the guinea pig 3β-hydroxysteroid dehydrogenase/Δ5-Δ4isomerase expressed in the adrenal gland and gonads. Program, 76th annual meeting of the Endocrinological Society, abstr 1192, p 498.

    Google Scholar 

  • Forest MG, Cathiard AM (1975) Pattern of plasma testosterone and Δ4-an-drostenedione in normal newborns: evidence for testicular activity at birth. J Clin Endocrinol Metab 41:977–984.

    Article  PubMed  CAS  Google Scholar 

  • Frasier SD, Gafford F, Horton R (1969) Plasma androgens in childhood and adolescence. J Clin Endocrinol Metab 29:1404–1408.

    Article  PubMed  CAS  Google Scholar 

  • Gosh D, Pletnev V, Zhu D-W, Wawrzak Z, Duax W, Pangborn W, Labrie F, Lin S-X (1995) Structure of human estrogenic 17β-hydroxysteroid dehydrogenase at 220A resolution. Structure 3:503–513.

    Article  Google Scholar 

  • Griffin JE, Wilson JD (1988) The testis. In: Browdy PK, Rosenberg LE (eds) Metabolic control and disease, 8th edn. Saunders, Philadelphia, pp 1535–1578.

    Google Scholar 

  • Guérin SL, Leclerc S, Verrault H, Labrie F, Luu-The V (1995) Overlapping cis-acting elements located in the first intron of the gene for type I 3β-hydroxysteroid dehydrogenase modulate its transcriptional activity. Mol Endocrinol 9:1583–1597.

    Article  PubMed  Google Scholar 

  • Heinrich UE, Bettendorf M, Vecsei P (1993) Male pseudohermaphroditism caused by nonsalt-losing congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase (3β-HSD) deficiency. J Steroid Biochem Mol Biol 45:83–85.

    Article  PubMed  CAS  Google Scholar 

  • Katsumata N, Tanae A, Yasunaga T, Horikawa R, Tanaka T, Hibi I (1995) A novel missense mutation in the type II 3β-hydroxysteroid dehydrogenase in a family with classical salt-wasting congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency. Hum Mol Genet 4:745–746.

    Article  PubMed  CAS  Google Scholar 

  • Keeney DS, Mason JI (1992a) Expression of testicular 3β-hydroxysteroid de-hydrogenase/Δ5-Δ4-isomerase: regulation by luteinizing hormone and for-skolin in Leydig cells of adult rats. Endocrinology 130:2007–2015.

    Article  PubMed  CAS  Google Scholar 

  • Keeney DS, Mason JI (1992b) Regulation of expression of 3β-hydroxysteroid dehydrogenase is mediated by cAMP in rat leydig cells and H540-rat Leydig tumor cells. J Steroid Biochem Mol Biol 43:915–922.

    Article  PubMed  CAS  Google Scholar 

  • Keeney DS, Naville D, Milewich L, Bartke A, Mason JI (1993) Multiple isoforms of 3β-hydroxysteroid dehydrogenase/Δ-Δ4-isomerase in mouse tissues — male-specific isoforms are expressed in the gonads and liver. Endocrinology 133:39–45.

    Article  PubMed  CAS  Google Scholar 

  • Kenny FM, Reynolds JW, Green OC (1971) Partial 3β-hydroxysteroid dehydrogenase (3β-HSD) deficiency in a family with congenital adrenal hyperplasia: evidence for increasing 3β-HSD activity with age. Pediatrics 48:756–765.

    PubMed  CAS  Google Scholar 

  • Krosowski Z (1992) 11β-Hydroxysteroid dehydrogenase and the short-chain alcohol dehydrogenase (SCAD) superfamily. Mol Cell Endocrinol 84:C25–C31.

    Article  Google Scholar 

  • Labrie C, Bélanger A, Labrie F (1988) Androgenic activity of dehydroepiandrosterone and androstenedione in the rat ventral prostate. Endocrinology 123:1412–1417.

    Article  PubMed  CAS  Google Scholar 

  • Labrie C, Simard J, Zhao HF, Bélanger A, Pelletier G, Labrie F (1989) Stimulation of androgen-dependent gene expression by the adrenal precursors dehydroepiandrosterone and androstenedione in the rat ventral prostate. Endocrinology 124:2745–2754.

    Article  PubMed  CAS  Google Scholar 

  • Labrie F (1991) Intracrinology. Mol Cell Endocrinol 78:C113–C118.

    Article  PubMed  CAS  Google Scholar 

  • Labrie F, Dupont A, Bélanger A (1985) Complete androgen blockade for the treatment of prostate cancer. In: de Vita VT, Hellman S, Rosenberg SA (eds) Important advances in oncology. Lippincott, Philadelphia, pp 193–217.

    Google Scholar 

  • Labrie F, Simard J, Luu-The V, Pelletier G (1994a) Molecular genetics structure-function relationships and tissue-specific expression and regulation of the 3β-HSD gene family. In: Bartke A (ed) Function of somatic cells in the testis Serono symposia. Springer, Berlin Heidelberg New York, pp 26–150.

    Google Scholar 

  • Labrie F, Simard J, Luu-The V, Pelletier G, Belghmi K, Bélanger A (1994b) Structure, regulation and role of 3β-hydroxysteroid dehydrogenase 17β-hydroxysteroid dehydrogenase and aromatase enzymes in formation of sex steroids in classical and peripheral intracrine tissues. In: Sheppard MC, Stewart PM (eds) Hormone-nuclear receptors interactions in health and disease. Bailliere Tindall, London, pp 451–474.

    Google Scholar 

  • Lachance Y, Luu-The V, Labrie C, Simard J, Dumont M, de Launoit Y, Guérin S, Leblanc G, Labrie F (1990) Characterization of human 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase gene and its expression in mammalian cells. J Biol Chem 265:20469–20475.

    PubMed  CAS  Google Scholar 

  • Lachance Y, Luu-The V, Verreault H, Dumont M, Rhéaume E, Leblanc G, Labrie F (1991) Structure of the human type II 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD) gene: adrenal and gonadal specificity. DNA Cell Biol 10:701–711.

    Article  PubMed  CAS  Google Scholar 

  • Lachance Y, Luu-The V, Labrie C, Simard J, Dumont M, de Launoit Y, Guérin S, Leblanc G, Labrie F (1992) Characterization of human 3β-hy-droxysteroid dehydrogenase/Δ5-Δ4-isomerase gene and its expression in mammalian cells (additions and corrections). J Biol Chem 267:3551.

    PubMed  CAS  Google Scholar 

  • Lebrethon MC, Jaillard C, Defayes G, Begeot M, Saez JM (1994a) Human cultured adrenal fasciculata-reticularis cells are targets for angiotensin-II: effects on cytochrome P450 cholesterol side-chain cleavage cytochrome P450 17α-hydroxylase and 3β-hydroxysteroid-dehydrogenase messenger ribonucleic acid and proteins and on steroidogenic responsiveness to corticotropin and angiotensin-II. J Clin Endocrinol Metab 78:1212–1219.

    Article  PubMed  CAS  Google Scholar 

  • Lebrethon MC, Jaillard C, Naville D, Begeot M, Saez JM (1994b) Regulation of corticotropin and steroidogenic enzyme mRNAs in human fetal adrenal cells by corticotropin angiotensin-II and transforming growth factor β 1. Mol Cell Endocrinol 106:137–143.

    Article  PubMed  CAS  Google Scholar 

  • Lorence MC, Corbin CJ, Kamimura N, Mahendroo MS, Mason JI (1990a) Structural analysis of the gene encoding human 3β-hydroxysteroid dehydrogenase/Δ-Δ4 isomerase. Mol Endocrinol 4:1850–1855.

    Article  PubMed  CAS  Google Scholar 

  • Lorence MC, Murry BA, Trant JM, Mason JI (1990b) Human 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase from placenta: expression in nonsteroidogenic cells of a protein that catalyzes the dehydrogenation/isomerization of C21 and C19 steroids. Endocrinology 126:2493–2498.

    Article  PubMed  CAS  Google Scholar 

  • Luu-The V, Coté J, Labrie F (1988) Purification and characterization of human placental 3β-hydroxysteroid dehydrogenase Δ5-Δ4 isomerase. Clin Invest Med 11:C32.

    Google Scholar 

  • Luu-The V, Lachance Y, Labrie C, Leblanc G, Thomas JL, Strickler RC, Labrie F (1989) Full length cDNA structure and deduced amino acid sequence of human 3β-hydroxy-5-ene steroid dehydrogenase. Mol Endocrinol 3:1310–1312.

    Article  PubMed  CAS  Google Scholar 

  • Luu-The V, Coté J, Labrie F (1990) Purification of microsomal and mitochondrial 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase from human placent. Ann N Y Acad Sci 595:386–388.

    Article  Google Scholar 

  • Luu-The V, Lachance Y, Leblanc G, Labrie F (1992) Human 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase: characterization of three additional related genes. Proceedings of the 74th annual meeting of the Endocrinological Society, abstr 1499.

    Google Scholar 

  • Martel C, Meiner MH, Gagne D, Simard J, Labrie F (1994) Widespread tissue distribution of steroid sulfatase 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD), 17β-HSD 5α-reductase and aromatase activities in the rhesus monkey. Mol Cell Endocrinol 104:103–111.

    Article  PubMed  CAS  Google Scholar 

  • Mason JI (1993) The 3β-hydroxysteroid dehydrogenase gene family of enzymes. Trends Endocrinol Metab 4:199–203.

    Article  CAS  Google Scholar 

  • Mébarki F, Sanchez R, Rhéaume E, Laflamme N, Simard J, Forest M, Bey-Omar F, David M, Labrie F, Morel Y (1995) Nonsalt-losing male pseudohermaphrodite due to novel homozygous N100S mutation in the type II 3β-hydroxysteroid dehydrogenase (HSD3B2) gene. J Clin Endocrinol Metab 80:2127–2134.

    Article  PubMed  Google Scholar 

  • Mendonca BB, Russell AJ, Vasconcelos Leite M, Arnhold IJ, Bloise W, Wajchenberg BL, Nicolau W, Sutcliffe RG, Wallace AM (1994) Mutation in 3β-hydroxysteroid dehydrogenase type II associated with pseudohermaphroditism in males and premature pubarche or cryptic expression in females. J Mol Endocrinol 12:119–122.

    Article  PubMed  CAS  Google Scholar 

  • Mesiano S, Coulter CL, Jaffe RB (1993) Localization of cytochrome P450 cholesterol side-chain cleavage cytochrome P450 17α-hydroxylase/17 20-lyase and 3β-hydroxysteroid dehydrogenase isomerase steroidogenic enzymes in human and rhesus monkey fetal adrenal glands: reappraisal of functional zonation. J Clin Endocrinol Metab 77:1184–1189.

    Article  PubMed  CAS  Google Scholar 

  • Milewich L, Shaw CE, Doody KM, Rainey WE, Mason JI, Carr BR (1991) 3β-Hydroxysteroid dehydrogenase activity in glandular and extraglandular human fetal tissues. J Clin Endocrinol Metab 73:1134–1140.

    Article  PubMed  CAS  Google Scholar 

  • Milewich L, Shaw CE, Mason JI, Carr BR, Blomquist CH, Thomas JL (1993) 3β-Hydroxy steroid dehydrogenase activity in tissues of the human fetus determined with 5α-androstane-3β17β-diol and dehydroepiandrosterone as substrates. J Steroid Biochem Mol Biol 45:525–537.

    Article  PubMed  CAS  Google Scholar 

  • Moghissi E, Ablan F, Horton R (1984) Origin of plasma androstanediol glucuronide in men. J Clin Endocrinol Metab 59:417–421.

    Article  PubMed  CAS  Google Scholar 

  • Moore JB, Smith GL (1992) Steroid hormone synthesis by a vaccinia enzyme: a new type of virus virulence factor [published erratum appears in EMBO J (1992) 11(9):3490]. EMBO J 11:1973–1980.

    PubMed  CAS  Google Scholar 

  • Morissette J, Rheaume E, Leblanc JF, Luu TV, Labrie F, Simard J (1995) Genetic linkage mapping of HSD3B1 and HSD3B2 encoding human types I and II 3β-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase close to D1S514 and the centromeric D1Z5 locus. Cytogenet Cell Genet 69:59–62.

    Article  PubMed  CAS  Google Scholar 

  • Morrison N, Nickson DA, McBride MW, Mueller UW, Boyd E, Sutcliffe RG (1991) Regional chromosomal assignment of human 3β-hydroxy-5-ene steroid dehydrogenase to 1p131 by non-isotopic in situ hybridisation. Hum Genet 87:223–235.

    Article  PubMed  CAS  Google Scholar 

  • Murono EP, Washburn AL (1990) Platelet derived growth factor inhibits 5α-reductase and Δ5-3β-hydroxysteroid dehydrogenase activities in cultured immature Leydig cells. Biochem Biophys Res Commun 169:1229–1234.

    Article  PubMed  CAS  Google Scholar 

  • Murono EP, Goforth DP, Washburn AL, Wu N (1993a) Evidence that biphasic effects of basic fibroblast growth factor on 5-ene-3β-hydroxysteroid dehydrogenase-isomerase activity in cultured immature Leydig cells are mediated by binding to heparan sulfate proteoglycans. J Steroid Biochem Mol Biol 46:557–563.

    Article  PubMed  CAS  Google Scholar 

  • Murono EP, Washburn AL, Goforth DP, Wu N (1993b) Effects of acidic fibroblast growth factor on 5-ene-3β-hydroxysteroid dehydrogenase-isomerase and 5 α-reductase activities and [125I]human chorionic gonadotrophin binding in cultured immature Leydig cells. J Steroid Biochem Mol Biol 45:477–483.

    Article  PubMed  CAS  Google Scholar 

  • Nahoul K, Perrin C, Leymarie P, Job JC (1989) Elevated levels of plasma 4-ene steroids in a case of congenital deficiency of 3β-hydroxysteroid dehydrogenase — Taux élevés des 4-ène stéroïdes plasmatiques dans un cas de déficit congénital en 3β-hydroxystéroïde déshydrogénase. Ann Endocrinol (Paris) 50:58–63.

    CAS  Google Scholar 

  • Naville D, Rainey WE, Mason JI (1991a) Corticotropin regulation of 3β-hy-droxysteroid dehydrogenase/Δ5-Δ4-isomerase in ovine adrenocortical cells: inhibition by transforming growth factor β. Mol Cell Endocrinol 75:257–263.

    Article  PubMed  CAS  Google Scholar 

  • Naville D, Rainey WE, Milewich L, Mason JI (1991b) Regulation of 3β-hy-droxysteroid dehydrogenase/Δ5-Δ4-isomerase expression by adrenocorticotropin in bovine adrenocortical cells. Endocrinology 128:139–145.

    Article  PubMed  CAS  Google Scholar 

  • New MI, White P, Pang S, Dupont B, Speiser PW (1989) The adrenal hyperplasias. In: Scriver CR, Beaudet A, Sly WS, Valle D (eds) The metabolic basis of inherited diseases. McGraw-Hill, New York, pp 1881–1917.

    Google Scholar 

  • Nickson DA, McBride MW, Zeinali S, Hawes CS, Petropoulos A, Mueller UW, Sutcliffe RG (1991) Molecular cloning and expression of human trophoblast antigen FDO161G and its identification as 3β-hydroxy-5-ene steroid dehydrogenase. J Reprod Fertil 93:149–156.

    Article  PubMed  CAS  Google Scholar 

  • Pang S, Levine LS, Stoner E, Opitz JM, Pollack MS, Dupont B, New MI (1983) Nonsalt-losing congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency with normal glomerulosa function. J Clin Endocrinol Metab 56:808–818.

    Article  PubMed  CAS  Google Scholar 

  • Payne AH, Sha LL (1991) Multiple mechanisms for regulation of 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase 17 alpha-hydroxylase/C17-20 lyase cytochrome P450 and cholesterol side-chain cleavage cytochrome P450 messenger ribonucleic acid levels in primary cultures of mouse Leydig cells. Endocrinology 129:1429–1435.

    Article  PubMed  CAS  Google Scholar 

  • Rainey WE, Naville D, Mason JI (1991) Regulation of 3β-hydroxysteroid dehydrogenase in adrenocortical cells: effects of angiotensin-II and transforming growth factor β. Endocr Res 17:281–296.

    Article  PubMed  CAS  Google Scholar 

  • Rheaume E, Lachance Y, Zhao HF, Breton N, Dumont M, de Launoit Y, Trudel C, Luu TV, Simard J, Labrie F (1991) Structure and expression of a new complementary DNA encoding the almost exclusive 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase in human adrenals and gonads. Mol Endocrinol 5:1147–1157.

    Article  PubMed  CAS  Google Scholar 

  • Rheaume E, Simard J, Morel Y, Mebarki F, Zachmann M, Forest MG, New MI, Labrie F (1992) Congenital adrenal hyperplasia due to point mutations in the type II 3β-hydroxysteroid dehydrogenase gene. Nat Genet 1:239–245.

    Article  PubMed  CAS  Google Scholar 

  • Rheaume E, Sanchez R, Simard J, Chang YT, Wang J, Pang S, Labrie F (1994) Molecular basis of congenital adrenal hyperplasia in two siblings with classical nonsalt-losing 3β-hydroxysteroid dehydrogenase deficiency. J Clin Endocrinol Metab 79:1012–1018.

    Article  PubMed  CAS  Google Scholar 

  • Rheaume E, Sanchez R, Mebarki F, Gagnon E, Carel JC, Chaussain JL, Morel Y, Labrie F, Simard J (1995) Identification and characterization of the G15D mutation found in a male patient with 3β-hydroxysteroid dehydrogenase (3β-HSD) deficiency: alteration of the putative NAD-binding domain of type II 3β-HSD. Biochemistry 34:2893–2900.

    Article  PubMed  CAS  Google Scholar 

  • Riley SC, Dupont E, Walton JC, Luu-The V, Labrie F, Pelletier G, Challis JR (1992) Immunohistochemical localization of 3β-hydroxy-5-ene-steroid denydroge-nase/Δ5-Δ4 isomerase in human placenta and fetal membranes throughout gestation. J Clin Endocrinol Metab 75:956–961.

    Article  PubMed  CAS  Google Scholar 

  • Riley SC, Bassett NS, Berdusco E, Yang K, Leystralantz C, Luu-The V, Labrie F, Challis G Jr (1993) Changes in the abundance of messenger RNA for type-I 3β-hydroxy-steroid dehydrogenase/Δ5-Δ4 isomerase in the human placenta and fetal membranes during pregnancy and labor. Gynecol Obstet Invest 35:199–203.

    Article  PubMed  CAS  Google Scholar 

  • Rogerson FM, Lehoux JG, Mason JI (1995) Expression and characterization of isoforms of 3β-hydroxysteroid dehydrogenase /Δ5-Δ4 isomerase in the hamster. J Steroid Biochem Mol Biol (in press).

    Google Scholar 

  • Rosenfield RL, Rich BH, Wolfsdorf JI, Cassorla F, Parks JS, Bongiovanni AM, Wu CH, Shackleton CH (1980) Pubertal presentation of congenital Δ5-3β-hydroxysteroid dehydrogenase deficiency. J Clin Endocrinol Metab 51:345–353.

    Article  PubMed  CAS  Google Scholar 

  • Russell AJ, Wallace AM, Forest MG, Donaldson MD, Edwards CR, Sutcliffe RG (1994) Mutation in the human gene for 3β-hydroxysteroid dehydrogenase type II leading to male pseudohermaphroditism without salt loss. J Mol Endocrinol 12:225–237.

    Article  PubMed  CAS  Google Scholar 

  • Sakai N, Tanaka M, Takahashi M, Fukada S, Mason JI, Nagahama Y (1994) Ovarian 3β-hydroxysteroid dehydrogenase/delta 5-4-isomerase of rainbow trout: its cDNA cloning and properties of the enzyme expressed in a mammalian cell. FEBS Lett 350:309–313.

    Article  PubMed  CAS  Google Scholar 

  • Sanchez R, de Launoit Y, Durocher F, Belanger A, Labrie F, Simard J (1994a) Formation and degradation of dihydrotestosterone by recombinant members of the rat 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase family. Mol Cell Endocrinol 103:29–38.

    Article  PubMed  CAS  Google Scholar 

  • Sanchez R, Mebarki F, Rheaume E, Laflamme N, Forest MG, Bey Omard F, David M, Morel Y, Labrie F, Simard J (1994b) Functional characterization of the novel L108 W and P186L mutations detected in the type II 3 b-hy-droxysteroid dehydrogenase gene of a male pseudohermaphrodite with congenital adrenal hyperplasia. Hum Mol Genet 3:1639–1645.

    Article  PubMed  CAS  Google Scholar 

  • Sanchez R, Rhéaume E, Laflamme N, Rosenfield RL, Labrie F, Simard J (1994c) Detection and functional characterization of the novel missense mutation Y254D in type II 3β-hydroxysteroid dehydrogenase (3β-HSD) gene of a female patient with nonsalt-losing 3β-HSD deficiency. J Clin Endocrinol Metab 78:561–578.

    Article  PubMed  CAS  Google Scholar 

  • Sasano H, Mason JI, Sasaki E, Yajima A, Kimura N, Namiki T, Sasano N, Nagura H (1990a) Immunohistochemical study of 3β-hydroxysteroid dehydrogenase in sex cord-stromal tumors of the ovary. Int J Gynecol Pathol 9:352–362.

    Article  PubMed  CAS  Google Scholar 

  • Sasano H, Mori T, Sasano N, Nagura H, Mason JI (1990b) Immunolocalization of 3β-hydroxysteroid dehydrogenase in human ovary. J Reprod Fertil 89:743–751.

    Article  PubMed  CAS  Google Scholar 

  • Sasano H, Nagura H, Harada N, Goukon Y, Kimura M (1994) Immunolocalization of aromatase and other steroidogenic enzymes in human breast disorders. Hum Pathol 25:530–535.

    Article  PubMed  CAS  Google Scholar 

  • Sauer LA, Chapman JC, Dauchy RT (1994) Topology of 3β-hydroxy-5-ene-steroid dehydrogenase/Δ5-Δ4-isomerase in adrenal cortex mitochondria and microsomes. Endocrinology 134:751–759.

    Article  PubMed  CAS  Google Scholar 

  • Scrutton NS, Berry A, Perham RN (1990) Redesign of the coenzyme specificity of a dehydrogenase by protein engineering. Nature 343:38–43.

    Article  PubMed  CAS  Google Scholar 

  • Simard J, de Launoit Y, Labrie F (1991a) Characterization of the structure-activity relationships of rat types I and II 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase by site-directed mutagenesis and expression in HeLa cells. J Biol Chem 266:14842–14845.

    PubMed  CAS  Google Scholar 

  • Simard J, Meiner MH, Breton N, Low KG, Zhao HF, Periman LM, Labrie F (1991b) Characterization of macaque 3β-hydroxy-5-ene steroid dehydrogenase/Δ5-Δ4 isomerase: structure and expression in steroidogenic and peripheral tissues in primate. Mol Cell Endocrinol 75:101–110.

    Article  PubMed  CAS  Google Scholar 

  • Simard J, Couët J, Durocher F, Labrie Y, Sanchez R, Breton N, Turgeon C, Labrie F (1993a) Structure and tissue-specific expression of a novel member of the rat 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD) family — the exclusive 3β-HSD gene expressed in the skin. J Biol Chem 268:19659–19668.

    PubMed  CAS  Google Scholar 

  • Simard J, Rhéaume E, Sanchez R, Laflamme N, de Launoit Y, Luu-The V, van Seters AP, Gordon RD, Bettendorf M, Heinrich U, Moshang T, New MI, Labrie F (1993b) Molecular basis of congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency. Mol Endocrinol 7:716–728.

    Article  PubMed  CAS  Google Scholar 

  • Simard J, Rhéaume E, Leblanc JF, Wallis SC, Joplin JF, Gilbey S, Allanson J, Mettler G, Bettendorf M, Heinrich UE, Labrie F (1994) Congenital adrenal hyperplasia caused by a novel homozygous frameshift mutation 273deltaAA in type II 3β-hydroxysteroid dehydrogenase gene (HSD3B2) in three male patients of Afghan/Pakistani origin. Hum Mol Genet 3:327–334.

    Article  PubMed  CAS  Google Scholar 

  • Simard J, Rheaume E, Mebarki F, Sanchez R, New M, Morel Y, Labrie F (1995) Molecular basis of 3β-hydroxysteroid dehydrogenase deficiency. J Steroid Biochem Mol Biol 53:127–138.

    Article  PubMed  CAS  Google Scholar 

  • Sordoillet C, Chauvin MA, de PE, Morera AM, Benahmed M (1991) Epidermal growth factor directly stimulates steroidogenesis in primary cultures of porcine Leydig cells: actions and sites of action. Endocrinology 128:2160–2168.

    Article  PubMed  CAS  Google Scholar 

  • Tajima T, Fujieda K, Nakae J, Shinohara N, Yoshimoto M, Baba T, Ei-ichi K, Igarashi Y, Oomura T (1995) Molecular analysis of type II 3β-hydoxysteroid dehydrogenase deficiency. Hum Mol Genet 4:969–971.

    Article  PubMed  CAS  Google Scholar 

  • Thomas JL, Myers RP, Strickler RC (1989) Human placental 3β-hydroxy-5-ene-steroid dehydrogenase and steroid 5→4-ene-isomerase: purification from mitochondria and kinetic profiles biophysical characterization of the purified mitochondrial and microsomal enzymes. J Steroid Biochem 33:209–217.

    Article  PubMed  CAS  Google Scholar 

  • Thomas JL, Myers RP, Rosik LO, Strickler RC (1990) Affinity alkylation of human placental 3β-hydroxy-5-ene-steroid dehydrogenase and steroid 5-4-ene-isomerase by 2 alpha-bromoacetoxyprogesterone: evidence for separate dehydrogenase and isomerase sites on one protein. J Steroid Biochem 36:117–123.

    Article  PubMed  CAS  Google Scholar 

  • Thomas JL, Strickler RC, Myers RP, Covey DF (1992) Affinity labeling of human placental 3β-hydroxy-Δ5-steroid dehydrogenase and steroid delta-isomerase: evidence for bifunctional catalysis by a different conformation of the same protein for each enzyme activity. Biochemistry 31:5522–5527.

    Article  PubMed  CAS  Google Scholar 

  • Thomas JL, Nash WE, Myers RP, Crankshaw MW, Strickler RC (1993) Affinity radiolabeling identifies peptides and amino acids associated with substrate binding in human placental 3β-hydroxy-Δ5-steroid dehydrogenase. J Biol Chem 268:18507–18512.

    PubMed  CAS  Google Scholar 

  • Trudel C, Couet J, Martel C, Labrie C, Labrie F (1991) Regulation of adrenal 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase expression and activity by adrenocorticotropin and corticosterone in the rat. Endocrinology 129:2077–2084.

    Article  PubMed  CAS  Google Scholar 

  • Tusie-Luna MT, Traktman P, White PC (1990) Determination of functional effects of mutations in the steroid 21-hydroxylase gene (CYP21) using recombinant vaccinia virus. J Biol Chem 265:20916–20922.

    PubMed  CAS  Google Scholar 

  • Turgeon C, Sanchez R, Rhéaume E, Labrie F, Simard J (1995) Characterization of the unique cofactor specificity of liver-specific rat 3β-hydroxysteroid dehydrogenase by side-rected mutagenesis. Proceedings of the 77th annual meeting of the Endocrinological Society, abstr P-3-633, p 619.

    Google Scholar 

  • Voutilainen R, Ilvesmaki V, Miettinen PJ (1991) Low expression of 3β-hy-droxy-5-ene steroid dehydrogenase gene in human fetal adrenals in vivo; adrenocorticotropin and protein kinase C-dependent regulation in adrenocortical cultures. J Clin Endocrinol Metab 72:761–767.

    Article  PubMed  CAS  Google Scholar 

  • Winter JSD, Hughes IA, Reyes FI (1976) Pituitary-gonadal relations in infancy 2. Patterns of serum gonadal steroid concentrations in man from birth to two years of age. J Clin Endocrinol Metab 42:679–686.

    Article  PubMed  CAS  Google Scholar 

  • Zachmann M, Vsllmin JA, Mürset G, Curtius HC, Prader A (1970) Unusual type of congenital adrenal hyperplasia probably due to deficiency of 3β-hy-droxysteroid dehydrogenase. Case report of a surviving girl and steroid studies. J Clin Endocrinol Metab 30:719–726.

    Article  PubMed  CAS  Google Scholar 

  • Zhao HF, Simard J, Labrie C, Breton N, Rhéaume E, Luu-The V, Labrie F (1989) Molecular cloning cDNA structure and predicted amino acid sequence of bovine 3β-hydroxy-5-ene steroid dehydrogenase/delta5-delta4 isomerase. FEBS Lett 259:153–157.

    Article  PubMed  CAS  Google Scholar 

  • Zhao HF, Rhéaume E, Trudel C, Couet J, Labrie F, Simard J (1990) Structure and sexual dimorphic expression of a liver-specific rat 3β-hydroxysteroid dehydrogenase/isomerase. Endocrinology 127:3237–3239.

    Article  PubMed  CAS  Google Scholar 

  • Zhao HF, Labrie C, Simard J, de Launoit Y, Trudel C, Martel C, Rhéaume E, Dupont E, Luu-The V, Pelletier G, Labrie F (1991) Characterization of rat 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase cDNAs and differential tissue-specific expression of the corresponding mRNAs in steroidogenic and peripheral tissues. J Biol Chem 266:583–593.

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. F. Labrie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Simard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. Luu-The
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Bélanger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Pelletier
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y. Morel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. F. Mebarki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R. Sanchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. F. Durocher
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. C. Turgeon
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Y. Labrie
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. E. Rheaume
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. C. Labrie
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Y. Lachance
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute of Medical Biochemistry, University of Oslo, P.O.Box 1112, Blindern, 0317, Oslo, Norway

    V. Hansson , F. O. Levy  & K. Taskén ,  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Labrie, F. et al. (1996). The 3β-Hydroxysteroid Dehydrogenase/Isomerase Gene Family: Lessons from Type II 3β-HSD Congenital Deficiency. In: Hansson, V., Levy, F.O., Taskén, K. (eds) Signal Transduction in Testicular Cells. Ernst Schering Research Foundation Workshop, vol 2/1996. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-03230-5_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-03230-5_10

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-03232-9

  • Online ISBN: 978-3-662-03230-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation