The steroidogenic acute regulatory protein is expressed in steroidogenic cells of the day-old brain

被引:23
作者
King, SR
Ginsberg, SD
Ishii, T
Smith, RG
Parker, KL
Lamb, DJ
机构
[1] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA
[2] Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA
[3] Nathan S Kline Inst Psychiat Res, Ctr Dementia Res, Orangeburg, NY 10962 USA
[4] NYU, Sch Med, Dept Psychiat, Orangeburg, NY 10962 USA
[5] NYU, Sch Med, Dept Physiol, Orangeburg, NY 10962 USA
[6] NYU, Sch Med, Dept Neurosci, Orangeburg, NY 10962 USA
[7] Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA
[8] Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA
关键词
D O I
10.1210/en.2003-1740
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Although recent research has focused on the fundamental role(s) of steroids synthesized de novo in the brain on development, the mechanism by which production of these neurosteroids is regulated remains unclear. Steroid production in peripheral tissues is acutely regulated by the steroidogenic acute regulatory (StAR) protein, which mediates the rate-limiting step in steroid biosynthesis: the intramitochondrial delivery of cholesterol to cytochrome P450scc for conversion to steroid. We recently demonstrated that StAR is present in discrete cell types in the adult brain, suggesting that neurosteroid production is mediated by StAR. Nevertheless, little is known regarding the presence of StAR in the developing brain. In the present study, the presence of StAR and for the first time, its homolog, the putative cholesterol transport protein metastatic lymph node 64 (MLN64), were defined in the neonatal mouse brain using immunocytochemical techniques. Both StAR and MLN64 were found to be present in the brain with staining patterns characteristic to each protein, indicating the authenticity of StAR and MLN64 immunoreactivity. Furthermore, we found MLN64 to be expressed in the adult brain as well, apparently at higher levels than StAR. Importantly, StAR protein is present in cells that also express P450scc. These data suggest that, as with the adult, neurosteroid production during development occurs through a StAR-mediated pathway.
引用
收藏
页码:4775 / 4780
页数:6
相关论文
共 43 条
  • [1] The steroidogenic acute regulatory protein homolog MLN64, a late endosomal cholesterol-binding protein
    Alpy, F
    Stoeckel, ME
    Dierich, A
    Escola, JM
    Wendling, C
    Chenard, MP
    Vanier, MT
    Gruenberg, J
    Tomasetto, C
    Rio, MC
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (06) : 4261 - 4269
  • [2] ANHOLT RRH, 1984, J NEUROSCI, V4, P593
  • [3] Expression of steroidogenic genes in maternal and extraembryonic cells during early pregnancy in mice
    Arensburg, J
    Payne, AH
    Orly, J
    [J]. ENDOCRINOLOGY, 1999, 140 (11) : 5220 - 5232
  • [4] The pathophysiology and genetics of congenital lipoid adrenal hyperplasia
    Bose, HS
    Sugawara, T
    Strauss, JF
    Miller, WL
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (25) : 1870 - 1878
  • [5] Mutations in the steroidogenic acute regulatory protein (StAR) in six patients with congenital lipoid adrenal hyperplasia
    Bose, HS
    Sato, S
    Aisenberg, J
    Shalev, SA
    Matsuo, N
    Miller, WL
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2000, 85 (10) : 3636 - 3639
  • [6] Targeted disruption of the mouse gene encoding steroidogenic acute regulatory protein provides insights into congenital lipoid adrenal hyperplasia
    Caron, KM
    Soo, SC
    Wetsel, WC
    Stocco, DM
    Clark, BJ
    Parker, KL
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (21) : 11540 - 11545
  • [7] Expression and modulation of steroidogenic acute regulatory protein messenger ribonucleic acid in rat cardiocytes and after myocardial infarction
    Casal, AJ
    Silvestre, JS
    Delcayre, C
    Capponi, AM
    [J]. ENDOCRINOLOGY, 2003, 144 (05) : 1861 - 1868
  • [8] Peripheral benzodiazepine receptors and mitochondrial function
    Casellas, P
    Galiegue, S
    Basile, AS
    [J]. NEUROCHEMISTRY INTERNATIONAL, 2002, 40 (06) : 475 - 486
  • [9] CLARK BJ, 1994, J BIOL CHEM, V269, P28314
  • [10] Neurosteroids: Biosynthesis and function of these novel neuromodulators
    Compagnone, NA
    Mellon, SH
    [J]. FRONTIERS IN NEUROENDOCRINOLOGY, 2000, 21 (01) : 1 - 56