Multiplicity of 17β-hydroxysteroid dehydrogenase
Kinetic analysis of enzymic activities: Prediction of multiple forms of 17β-hydroxysteroid dehydrogenase

https://doi.org/10.1016/0960-0760(95)00200-6Get rights and content

Abstract

An overview of the application of kinetic methods to the delineation of 17β-hydroxysteroid dehydrogenase (17β-HSD) heterogeneity in mammalian tissues is presented. Early studies of 17β-HSD activity in animal liver and kidney subcellular fractions were suggestive of multiple forms of the enzyme. Subsequently, detailed characterization of activity in cytosol and subcellular membrane fractions of human placenta, with particular emphasis on inhibition kinetics, yielded evidence of two kinetically-differing forms of 17β-HSD in that organ. Gene cloning and transfection experiments have confirmed the identity of these two proteins as products of separate genes. 17β-HSD type 1 is a cytosolic enzyme highly specific for C18 steroids such as 17β-estradiol (E2) and estrone (E1). 17β-HSD type 2 is a membrane bound enzyme reactive with testosterone (T) and androstenedione (A), as well as E2 and E1. Useful parameters for the detection of multiple forms of 17β-HSD appear to be the E2T activity ratio, NAD/NADP activity ratios, steroid inhibitor specificity and inhibition patterns over a wide range of putative inhibitor concentrations. Evaluation of these parameters for microsomes from samples of human breast tissue suggests the presence of 17β-HSD type 2. The 17β-HSD enzymology of human testis microsomes appears to differ from placenta. Analysis of human ovary indicates granulosa cells are particularly enriched in the type 1 enzyme with type 2-like activity in stroma/theca. Mouse ovary appears to contain forms of 17β-HSD which differ from 17β-HSD type 1 and type 2 in their kinetic properties.

References (44)

  • P. Leinonen

    17β-Oxidation of estradiol and testosterone in the human testis

    J. Steroid Biochem.

    (1982)
  • R.L. Barbieri

    Human ovarian 17-ketosteroid reductase: Unique characteristics of the granulosa-luteal cell and stromal enzyme

    Am. J. Obstet. Gynec.

    (1992)
  • C. Sawetawan et al.

    Compartmentalization of type I 17β-hydroxysteroid oxidoreductase in the human ovary

    Molec. Cell. Endocr.

    (1994)
  • C.H. Blomquist et al.

    A comparison of 17β-hydroxysteroid oxidoreductase type 1 and type 2 activity of cytosol and microsomes from human term placenta, ovarian stroma and granulosa-luteal cells

    J. Steroid Biochem. Molec. Biol.

    (1994)
  • L. Milewich et al.

    17β-Hydroxysteroid oxidoreductase: a ubiquitous enzyme

    Interconversion of estrone and estradiol-17β in BALBc mouse tissues

    Metabolism

    (1985)
  • C.H. Blomquist et al.

    Placental 17β-hydroxysteroid oxidoreductase, lactate dehydrogenase and malate dehydrogenase during the latter half of pregnancy in the mouse

    J. Steroid Biochem. Molec. Biol.

    (1993)
  • L.E. Bolcsak et al.

    Purification of mouse liver benzene dihydrodiol dehydrogenases

    J. Biol. Chem.

    (1983)
  • H. Sawada et al.

    Mouse liver dihydrodiol dehydrogenases

    Biochem. Pharmac.

    (1988)
  • K.J. Ryan et al.

    The interconversion of estrone and estradiol by human tissue slices

    Endocrinology

    (1953)
  • Y. Aoshima et al.

    Activity, intracellular distribution and some properties of 17β-hydroxy-C19-steroid dehydrogenases in liver and kidney

    Endocrinology

    (1963)
  • L. Milewich et al.

    Activity of 17β-hydroxysteroid oxidoreductase in tissues of the human fetus

    J. Endocr.

    (1989)
  • Y. Tremblay et al.

    Regulation of the gene for estrogenic 17-ketosteroid reductase lying on chromosome 17cen-q25

    J. Biol. Chem.

    (1989)
  • Cited by (43)

    • A novel 17β-hydroxysteroid dehydrogenase in Rhodococcus sp. P14 for transforming 17β-estradiol to estrone

      2017, Chemico-Biological Interactions
      Citation Excerpt :

      17β-HSD from mammalian was well studied. Previously, many of 17β-HSDs from various species were identified and successfully cloned in several mammalian cells [33–36]. In particular, the role and the mechanism of 17β-HSDs in human being is clear nowadays.

    • Genetics of PCOS: A systematic bioinformatics approach to unveil the proteins responsible for PCOS

      2016, Genomics Data
      Citation Excerpt :

      The type I 3β-HSD isoenzyme is expressed in placenta and peripheral tissues, whereas the type II 3β-HSD isoenzyme is expressed in the adrenal gland, ovary, and testis. ( HSD3B) deficiency in hyperandrogenic females (HF) is related to insulin-resistant polycystic ovary syndrome (PCOS) [5]. The Steroidogenic Acute Regulatory protein is also known as StAR.

    • Genetic Basis of Gonadal and Genital Development

      2015, Endocrinology: Adult and Pediatric
    • Genetic Basis of Gonadal and Genital Development

      2010, Endocrinology: Adult and Pediatric, Sixth Edition
    • Steroid-converting enzymes in human ovarian carcinomas

      2009, Molecular and Cellular Endocrinology
    View all citing articles on Scopus
    View full text