Structure and tissue-specific expression of 3ß-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase genes in human and rat classical and peripheral steroidogenic tissues

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Abstract

The enzyme 3ß-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase (3ß-HSD) catalyzes the oxidation and isomerization of 5-ene-3ß-hydroxypregnene and 5-ene-hydroxyandrostene steroid precursors into the corresponding 4-ene-ketosteroids necessary for the formation of all classes of steroid hormones. We have recently characterized two types of human 3ß-HSD cDNA clones and the corresponding genes which encode deduced proteins of 371 and 372 amino acids, respectively, and share 93.5% homology. The human 3ß-HSD genes containing 4 exons were assigned by in situ hybridization to the p11–p13 region of the short arm of chromosome 1. We have also recently elucidated the structure of three types of rat 3ß-HSD cDNAs as well as that of one type of 3ß-HSD from bovine and macaque ovary λgt11 cDNA libraries which all encode 372 amino acid proteins. The human type I 3ß-HSD is the almost exclusive mRNA species detected in the placenta and skin, while the human type II is the predominant mRNA species in the adrenals, ovaries and testes. The predicted rat type I and type II 3ß-HSD proteins expressed in adrenals, gonads and adipose tissue share 94% homology while they share 80% similarity with the liver-specific type III 3ß-HSD. Transient expression of human type I and type II as well as rat type I and type II 3ß-HSD cDNAs in Hela human cervical carcinoma cells reveals that 3ß-ol dehydrogenase and 5-ene-4-ene isomerase activities reside within a single protein and these cDNAs encode functional 3ß-HSD proteins that are capable of converting 3ß-hydroxy-5-ene-steroids into 3-keto-4-ene derivatives as well as the interconversion of 3ß-hydroxy and 3-keto-5α-androstane steroids. We have found that the rat type III mRNA species was below the detection limit in intact female liver while, following hypophysectomy, its accumulation increased to 55% of the levels measured in intact or HYPOX male rats, an increase which can be blocked by administration of ovine prolactin (oPRL). In addition, in female rats, treatment with oPRL for 10 days starting 15 days after HYPOX, markedly decreased ovarian 3ß-HSD mRNA accumulation accompanied by a similar decrease in 3ß-HSD activity and protein levels. Treatment with the gonadotropin hCG reversed the potent inhibitory effect of oPRL on these parameters and stimulated 3ß-HSD mRNA levels in ovarian interstitial cells. In intact females, hCG exerted marked trophic effects on rat corpora lutea with an increase in total ovarian 3ß-HSD expression and activity. We have also shown that treatment with hCG for 15 days in intact male rats caused a marked increase in testicular 3ß-HSD expression and activity while glucocorticoids exerted inhibitory effects on these parameters. We have also observed that the ontogeny of 3ß-HSD expression in human and rat adrenal gland, testis and ovary is closely correlated with steroid hormone biosynthesis, thus suggesting that regulation of the expression of 3ß-HSD is a limiting step in the biosynthesis of steroids in these tissues.

References (51)

  • P. Klein et al.

    The detection and classification of membrane-spanning proteins

    Biochim. Biophys. Acta

    (1985)
  • D. Eisenberg et al.

    Analysis of membrane and surface protein sequences with the hydrophobic moment plot

    J. Molec. Biol.

    (1984)
  • P.E. Pochi et al.

    Sebaceous gland response in man to the administration of testosterone, Δ4-androstenedione, and dehydro-isoandrosterone

    J. Invest. Dermat.

    (1969)
  • J. Simard et al.

    Characterization of the structure-activity relationships of rat type I and type II 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase by site directed mutagenesis and expression in HeLa cells

    J. Biol. Chem.

    (1991)
  • F. Labrie et al.

    Complete androgen blockade for the treatment of prostate cancer

  • B. Tamaoki

    Steroidogenesis and cell structures. Biochemical pursuit of sites of steroid biosynthesis

    J. Steroid Biochem.

    (1973)
  • D. Lacoste et al.

    Biosynthesis and degradation of androgens in human prostatic cancer cell lines

  • A.M. Bongiovanni et al.

    The adrenogenital syndrome with deficiency of 3ß-hydroxysteroid dehydrogenase

    J. Clin. INvest.

    (1962)
  • V. Luu-The et al.

    Full length cDNA structuree and deduced amino acid sequence of human 3ß-hydroxy-5-ene steroid dehydrogenase

    Molec. Endocr.

    (1989)
  • V. Luu-The et al.

    Purification of mitochondrial 3ß-hydroxysteroid dehydrogenase/Δ54 isomerase from human placenta

    Ann. N.Y. Acad. Sci.

    (1990)
  • H.F. Zhao et al.

    Structure and sexual dimorphic expression of a liver-specific rat 3ß-hydroxysteroid dehydrogenase/isomerase

    Endocrinology

    (1990)
  • E. Rhéaume et al.

    Structure and expression of a new cDNA encoding the major 3ß-hydroxysteroid dehydrogenase/Δ54 isomerase present in human adrenals and gonalds

    Molec. Endocr.

    (1991)
  • D. Bérubé et al.

    Assignment of the human 3ß-hydroxysteroid dehydrogenase gene to the p13 band of chromosome 1

    Cytogen Cell Genet.

    (1989)
  • E. Dupont et al.

    Ontogeny of 3ß-hydroxysteroid dehydrogenase0/Δ54 isomerase (3ß-HSD) in human testis as studied by immunocytochemistry

    J. Androl.

    (1991)
  • E. Dupont et al.

    Immunochemical localization of 3ß-hydroxysteroid dehydrogenase/Δ54 isomerase (3ß-HSD) in human ovary

    J. Clin. Endocr. Metab.

    (1992)
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