Replacement of Alanine with Asparagic Acid at Position 203 in Human Steroidogenic Acute Regulatory Protein Impairs the Ability to Enhance Steroidogenesis in vitro

• KATSUMATA Noriyuki

  Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development

• HORIKAWA Reiko

  Division of Endocrinology and Metabolism, National Center for Child Health and Development

• TANAKA Toshiaki

  Department of Clinical Laboratory Medicine, National Center for Child Health and Development

Abstract

Steroidogenic acute regulatory protein (StAR) is a 30-kDa phosphorylated protein that rapidly appears in mitochondria of steroidogenic cells following tropic stimulation, and is required in the acute regulation of steroidogenesis. It was reported that mutations in the STAR gene encoding StAR cause congenital lipoid adrenal hyperplasia (CLAH), an autosomal recessive disorder characterized by impaired synthesis of all adrenal and gonadal steroid hormones. We previously reported a D203A polymorphism in the STAR gene in Japanese patients with CLAH as well as in normal Japanese subjects. In the present study, we analyzed the ability of the A203 StAR and D203 StAR to stimulate steroidogenesis using the in vitro functional expression system. The A203 StAR caused a twelve-fold increase in pregnenolone secretion over COS-1 cells transfected with an NH₂-cholesterol side-chain cleavage enzyme (P450scc)-adrenodoxin reductase-adrenodoxin-COOH fusion protein expressing plasmid (F2) and an empty vector, whereas the D203 StAR increased pregnenolone production no more than threefold. Western blot analysis detected mainly two species of StAR consisting of the 37-kDa precursor and the 30-kDa mature form. Together, these results indicate that the alanine at position 203 in human StAR is functionally important and that the D203 StAR is extremely unlikely to be a polymorphism.<br>

Journal

• Endocrine Journal

  Endocrine Journal 53 (3), 427-431, 2006

  The Japan Endocrine Society

Keywords

• Steroidogenic acute regulatory protein (StAR)
• Congenital lipoid adrenal hyperplasia
• Mutation

Details

• CRID: 1390282681274106624
• NII Article ID: 10018178263
• NII Article ID: 130004443241
• NII Book ID: AA10901436
• DOI: 10.1507/endocrj.k05-174
• ISSN: 13484540
• ISSN: 09188959
• Web Site: http://www.jstage.jst.go.jp/article/endocrj/53/3/53_3_427/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2007068935
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
• Abstract License Flag: Disallowed