title: Fetal testosterone influences sexually dimorphic gray matter in the human brain.
abstract: In nonhuman species, testosterone is known to have permanent organizing effects early in life that predict later expression of sex differences in brain and behavior. However, in humans, it is still unknown whether such mechanisms have organizing effects on neural sexual dimorphism. In human males, we show that variation in fetal testosterone (FT) predicts later local gray matter volume of specific brain regions in a direction that is congruent with sexual dimorphism observed in a large independent sample of age-matched males and females from the NIH Pediatric MRI Data Repository. Right temporoparietal junction/posterior superior temporal sulcus (RTPJ/pSTS), planum temporale/parietal operculum (PT/PO), and posterior lateral orbitofrontal cortex (plOFC) had local gray matter volume that was both sexually dimorphic and predicted in a congruent direction by FT. That is, gray matter volume in RTPJ/pSTS was greater for males compared to females and was positively predicted by FT. Conversely, gray matter volume in PT/PO and plOFC was greater in females compared to males and was negatively predicted by FT. Subregions of both amygdala and hypothalamus were also sexually dimorphic in the direction of Male > Female, but were not predicted by FT. However, FT positively predicted gray matter volume of a non-sexually dimorphic subregion of the amygdala. These results bridge a long-standing gap between human and nonhuman species by showing that FT acts as an organizing mechanism for the development of regional sexual dimorphism in the human brain.
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge CB2 8AH, UK. ml437@cam.ac.uk
authors.forename: Michael V
authors.initials: MV
authors.lastname: Lombardo
authors.forename: Emma
authors.initials: E
authors.lastname: Ashwin
authors.forename: Bonnie
authors.initials: B
authors.lastname: Auyeung
authors.forename: Bhismadev
authors.initials: B
authors.lastname: Chakrabarti
authors.forename: Kevin
authors.initials: K
authors.lastname: Taylor
authors.forename: Gerald
authors.initials: G
authors.lastname: Hackett
authors.forename: Edward T
authors.initials: ET
authors.lastname: Bullmore
authors.forename: Simon
authors.initials: S
authors.lastname: Baron-Cohen
mesh_terms: D019521:Body Patterning / Q000502:physiology; D001921:Brain / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D005260:Female; D005333:Fetus / Q000196:embryology* / Q000378:metabolism; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008297:Male; D012727:Sex Characteristics; D012733:Sex Differentiation / Q000502:physiology*; D013739:Testosterone / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D013995:Time
chemical_list: D013739:Testosterone