title: Growth of white matter in the adolescent brain: role of testosterone and androgen receptor.
abstract: The growth of white matter during human adolescence shows a striking sexual dimorphism; the volume of white matter increases with age slightly in girls and steeply in boys. Here, we provide evidence supporting the role of androgen receptor (AR) in mediating the effect of testosterone on white matter. In a large sample of typically developing adolescents (n = 408, 204 males), we used magnetic resonance imaging and acquired T1-weighted and magnetization transfer ratio (MTR) images. We also measured plasma levels of testosterone and genotyped a functional polymorphism in the AR gene, namely the number of CAG repeats in exon 1 believed to be inversely proportional to the AR transcriptional activity. We found that the testosterone-related increase of white-matter volume was stronger in male adolescents with the lower versus higher number of CAG repeats in the AR gene, with testosterone explaining, respectively, 26 and 8% of variance in the volume. The MTR results suggest that this growth is not related to myelination; the MTR decreased with age in male adolescents. We speculate that testosterone affects axonal caliber rather than the thickness of the myelin sheath.
authors.affiliation: Brain and Body Centre, University of Nottingham, Nottingham NG72RD, United Kingdom.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Perrin
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Hervé
authors.forename: Gabriel
authors.initials: G
authors.lastname: Leonard
authors.forename: Michel
authors.initials: M
authors.lastname: Perron
authors.forename: G Bruce
authors.initials: GB
authors.lastname: Pike
authors.forename: Alain
authors.initials: A
authors.lastname: Pitiot
authors.forename: Louis
authors.initials: L
authors.lastname: Richer
authors.forename: Suzanne
authors.initials: S
authors.lastname: Veillette
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Pausova
authors.forename: Tomás
authors.initials: T
authors.lastname: Paus
mesh_terms: D000293:Adolescent; D000375:Aging / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D048429:Cell Size; D002648:Child; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009186:Myelin Sheath / Q000378:metabolism / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000648:ultrastructure; D009434:Neural Pathways / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D012727:Sex Characteristics; D013739:Testosterone / Q000097:blood* / Q000502:physiology; D018911:Trinucleotide Repeats / Q000235:genetics
chemical_list: D011944:Receptors, Androgen; D013739:Testosterone
references.citation: Trends Neurosci. 1995 Oct;18(10):459-61
references.pmid: 8545913
references.citation: Neurology. 1999;53(5 Suppl 3):S3-7
references.pmid: 10496203
references.citation: Nature. 1991 Jul 4;352(6330):77-9
references.pmid: 2062380
references.citation: AJNR Am J Neuroradiol. 2001 Jun-Jul;22(6):1137-42
references.pmid: 11415910
references.citation: Eur J Clin Pharmacol. 2003 Nov;59(8-9):571-7
references.pmid: 13680032
references.citation: Neuroimage. 2007 Jul 15;36(4):1065-73
references.pmid: 17513132
references.citation: J Comp Neurol. 2003 Jul 21;462(2):144-52
references.pmid: 12794739
references.citation: J Steroid Biochem. 1982 Jun;16(6):801-10
references.pmid: 7202083
references.citation: Hum Brain Mapp. 2007 Jun;28(6):502-18
references.pmid: 17469173
references.citation: Trends Cogn Sci. 2005 Feb;9(2):60-8
references.pmid: 15668098
references.citation: Cereb Cortex. 2001 Jun;11(6):552-7
references.pmid: 11375916
references.citation: Semin Reprod Med. 2001;19(1):103-9
references.pmid: 11394198
references.citation: Exp Cell Res. 2007 Jun 10;313(10):2110-20
references.pmid: 17451679
references.citation: Magn Reson Med. 2008 Feb;59(2):268-77
references.pmid: 18228601
references.citation: J Neuroendocrinol. 1993 Aug;5(4):357-63
references.pmid: 8401559
references.citation: J Cell Biol. 1996 Nov;135(3):711-24
references.pmid: 8909545
references.citation: Nat Clin Pract Urol. 2007 Mar;4(3):161-6
references.pmid: 17347661
references.citation: Ann Neurol. 2004 Sep;56(3):407-15
references.pmid: 15349868
references.citation: J Neurochem. 2001 Aug;78(4):854-61
references.pmid: 11520906
references.citation: Hum Mol Genet. 2000 Jan 22;9(2):267-74
references.pmid: 10607837
references.citation: Cell Mol Life Sci. 2008 Mar;65(5):777-97
references.pmid: 18038216
references.citation: Am J Psychiatry. 1988 Apr;145(4):487-90
references.pmid: 3279830
references.citation: J Am Acad Child Adolesc Psychiatry. 2001 Apr;40(4):443-9
references.pmid: 11314570
references.citation: Neurotherapeutics. 2007 Jul;4(3):460-84
references.pmid: 17599712
references.citation: J Youth Adolesc. 1988 Apr;17(2):117-33
references.pmid: 24277579
references.citation: Magn Reson Med. 1996 Jul;36(1):95-103
references.pmid: 8795027
references.citation: J Biol Chem. 1999 Jul 16;274(29):20229-34
references.pmid: 10400640
references.citation: Proc Natl Acad Sci U S A. 1987 May;84(10):3472-6
references.pmid: 3472217
references.citation: Radiology. 1994 Aug;192(2):521-9
references.pmid: 8029426