Elsevier

Vitamins & Hormones

Volume 51, 1995, Pages 339-370
Vitamins & Hormones

Transcriptional Regulation of the Genes Encoding the Cytochrome P-450 Steroid Hydroxylases

https://doi.org/10.1016/S0083-6729(08)61044-4Get rights and content

Publisher Summary

This chapter discusses the transcriptional regulation of the genes encoding the cytochrome P-450 steroid hydroxylases. Steroid hormones are essential regulators of such diverse processes as accommodation to stress, carbohydrate metabolism, fluid and electrolyte balance, and reproduction. All endogenous steroids are derived from cholesterol and, therefore, have the cyclopentanoperhydrophenanthrene nucleus as a part of their basic structure. Modifications to this basic nucleus generate specific ligands for the members of the nuclear receptor family of transcription factors, accounting for their specific actions in different target tissues. Pregnenolone and 17α-hydroxypregnenolone are converted into progesterone and 17α-hydroxyprogesterone, respectively, by the microsoma1 enzyme 3β-hydroxysteroid dehydrogenase, which is one of the few noncytochrome P-450 steroid-biosynthetic enzymes and essential for the production of all major physiological steroid hormones. The expression of these functionally distinct CYP11B genes in the appropriate cortical zones plays an essential role in the gland's ability to separately regulate the biosynthesis of mineralocorticoids and glucocorticoids.

References (121)

  • N. Kagawa et al.

    Purification and characterization of a transcription factor which appears to regulate cAMP responsiveness of the human CYP21B gene.

    J. Biol. Chem.

    (1992)
  • N. Kagawa et al.

    A cAMP-regulatory sequence (crsl) of cypl7 is a cellular target for the homeodomain protein pbx.

    J. Biol. Chem.

    (1994)
  • A. Kakizuka et al.

    Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML.

    Cell

    (1991)
  • M.P. Kamps et al.

    A new homeobox gene contributes to the DNA binding domain of the t(1;19) translocation protein in pre-B. ALL.

    Cell

    (1990)
  • G.B. Kletter et al.

    Congenital adrenal hypoplasia and isolated gonadotropin deficiency.

    Trends Endocrinol. Metab.

    (1991)
  • K.E. Krueger et al.

    Peripheral-type benzodiazepine receptors mediate translocation of cholesterol from outer to inner membranes in adrenocortical cells.

    J. Biol. Chem.

    (1990)
  • F. Labrie et al.

    Structure, function, and tissue-specific gene expression of 3 beta-hydroxysteroid dehydro-genase/5-ene-4-ene isomerase enzymes in classical and peripheral intracrine steroidogenic tissues.

    J. Steroid Biochem. Mol. Biol.

    (1992)
  • M.E. Lauber et al.

    Regulation of CYP11A gene expression in bovine ovarian granulosa cells in primary culture by cAMP and phorbol esters is conferred by a common cisacting element.

    Mol. Cell. Endocrinol.

    (1993)
  • X. Luo et al.

    A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation.

    Cell

    (1994)
  • S.H. Mellon et al.

    Neurosteroid biosynthesis: Genes for adrenal steroidogenic enzymes are expressed in the brain.

    Brain Res.

    (1993)
  • J. Milbrandt

    Nerve growth factor induces a gene homologous to the glucocorticoid receptor gene.

    Neuron

    (1988)
  • D.S. Milstone et al.

    An element regulating adrenal-specific steroid 21-hydroxylase expression is located within the Sip gene.

    J. Biol. Chem.

    (1992)
  • E. Mornet et al.

    Characterization of two genes encoding human steroid 11**-hydroxylase (P45011**).

    J. Biol. Chem.

    (1989)
  • K. Morohashi et al.

    A common trans-acting factor, Ad4BP, to the promoters of steroidogenic P450s.

    J. Biol. Chem.

    (1992)
  • K.L. Parker et al.

    Transcriptional regulation of the adrenal steroidogenic enzymes.

    Trends Endocrinol. Metab.

    (1993)
  • S.M. Pfeifer et al.

    Sterol carrier protein 2: A role in steroid hormone synthesis?

    J. Steroid Biochem. Mol. Biol.

    (1993)
  • L.A. Pon et al.

    Acute ACTH regulation of adrenal corticosteroid biosynthesis. Rapid accumulation of a phosphoprotein.

    J. Biol. Chem.

    (1986)
  • D.A. Rice et al.

    A cAMP-responsive element regulates expression of the mouse steroid lip-hydroxylase gene.

    J. Biol. Chem.

    (1989)
  • RiceD.A. et al.

    Analysis of the promoter region of the gene encoding mouse cholesterol side-chain cleavage enzyme.

    J. Biol. Chem.

    (1990)
  • P. Robel et al.

    Neurosteroids: Biosynthesis and function.

    Trends Endocrinol. Metab.

    (1994)
  • W.-H. Shen et al.

    Nuclear receptor steroidogenic factor 1 regulates MIS gene expression: A link to the sex determination cascade.

    Cell

    (1994)
  • ArmstrongD.T. et al.

    Estrogen biosynthesis in the ovaries and testes.

    Adv. Sex Horm. Res.

    (1977)
  • M. Bakke et al.

    A novel 3′,5′-cyclic adenosine monaphosphate-responsive sequence in the bovine CYP17 gene is a target of negative regulation by protein kinase C.

    Mol. Endocrinol.

    (1992)
  • M. Bakke et al.

    Mutually exclusive interactions of two nuclear receptors determine activity of a cyclic adenosine 3′,5′-monophosphate-responsive sequence in the bovine CYP17 gene.

    Mol. Endocrinol.

    (1995)
  • K.M. Barnhart et al.

    The orphan nuclear receptor, steroidogenic factor-1, regulates the glycoprotein hormone alpha-subunit gene in pituitary go-nadotropes.

    Mol. Endocrinol.

    (1994)
  • P.Q. Barrett et al.

    The role of calcium in angiotensin II-mediated aldosterone secretion.

    Endocr. Rev.

    (1989)
  • A. Bogerd et al.

    Identification and characterization of two upstream elements that regulate adrenocortical expression of steroid ll**-hydroxylase.

    Mol. Endocrinol.

    (1990)
  • S.T. Brentano et al.

    Tissue-specific, cAMP-induced, and phorbol ester repressed expression from the human P450cl7 promoter in mouse cells.

    Mol. Endocrinol.

    (1990)
  • M.R. Briggs et al.

    Purification and biochemical characterization of the promoter-specific transcription factor, Spl.

    Science

    (1986)
  • S.E. Bulun et al.

    Use of tissue-specific promoters in the regulation of aromatase cytochrome P450 gene expression in human testicular and ovarian sex cord tumors, as well as in normal fetal and adult gonads.

    J. Clin. Endocrinol. Metab.

    (1994)
  • J.C. Chrivia et al.

    Phosphorylated CREB binds specifically to the nuclear protein CBP.

    Nature

    (1993)
  • J.W. Clemens et al.

    Steroidogenic factor 1 binding and transcriptional activity of the cholesterol side chain cleavage promoter in rat granulosa cells.

    Endocrinology

    (1994)
  • A.J. Cooney et al.

    Chicken ovalbumin upstream promoter transcription factor (COUP-TF) dimers bind to different GGTCA response elements, allowing COUP-TF to repress hormonal induction of the vitamin D3, thyroid hormone, and retinoic acid receptors.

    Mol. Cell. Biol.

    (1992)
  • K. Damm

    ErbA: Tumor suppressor turned oncogene?

    FASEB J.

    (1993)
  • I.J. Davis et al.

    Endocrine and neurogenic regulation of the orphan nuclear receptors Nur77 and Nurr-1 in the adrenal glands.

    Mol. Cell. Biol.

    (1994)
  • L.J. Domalik et al.

    Different isozymes of mouse 11**-hydroxylase produce mineralocorticoids and glucocorticoids.

    Mol. Endocrinol.

    (1991)
  • R.M. Evans

    The steroid and thyroid hormone receptor superfamily.

    Science

    (1988)
  • S.L. Fitzpatrick et al.

    Cis-acting elements of the rat aromatase promoter required for cyclic adenosine 3′,5′-monophosphate induction in ovarian granulosa cells and constitutive expression in R2C Leydig cells.

    Mol. Endocrinol.

    (1993)
  • S.L. Fitzpatrick et al.

    Identification of a cyclic adenosine 3′,5′-monophosphate-response element in the rat promoter that is required for transcriptional activation in rat granulosa cells and R2C Leydig cells.

    Mol. Endocrinol.

    (1994)
  • M. Gamier et al.

    The polypeptide diazepam-binding inhibitor and a higher affinity mitochondrial peripheral-type benzodiazepine receptor sustain constitutive steroidogenesis in the R2C Leydig tumor cell line.

    J. Biol. Chem.

    (1994)
  • Cited by (100)

    • Review on crosstalk and common mechanisms of endocrine disruptors: Scaffolding to improve PBPK/PD model of EDC mixture

      2017, Environment International
      Citation Excerpt :

      The enzymes that are responsible for the biosynthesis of these hormones mainly involved CYPs, HSDs and steroid reductases (Miller, 1988). The molecular mechanisms involved in biosynthesis are transfer of cholesterol to inner mitochondrial membrane by regulatory protein StAR (Manna and Stocco, 2005) and conversion of cholesterol to pregnenolone by CYP11A or CYP450scc (Parker and Schimmer, 1995; Manna and Stocco, 2005). Subsequent action of CYP17A and HSD enzyme accomplishes the glucocorticoid synthesis.

    • Steroid 21-hydroxylase deficiency in congenital adrenal hyperplasia

      2017, Journal of Steroid Biochemistry and Molecular Biology
    View all citing articles on Scopus
    View full text