title: Kisspeptin Expression in the Human Infundibular Nucleus in Relation to Sex, Gender Identity, and Sexual Orientation.
abstract: Since the discovery of its central role in reproduction, our functional neuroanatomical knowledge of the hypothalamic kisspeptin system is predominantly based on animal studies. Although sex differences in kisspeptin expression have been shown in humans in adulthood, the developmental origin of this sex difference is unknown.
  
  
  
  Our objectives were to determine the following: 1) when during development the sex difference in kisspeptin expression in the infundibular nucleus would emerge and 2) whether this sex difference is related to sexual orientation or transsexuality.
  
  
  
  Postmortem hypothalamic tissues were collected by The Netherlands Brain Bank, and sections were stained for kisspeptin by immunohistochemistry.
  
  
  
  Hypothalami of 43 control subjects were categorized into three periods: infant/prepubertal (six girls, seven boys), adult (11 women, seven men), and elderly (six aged women, six aged men). Eight male-to-female (MTF) transsexuals, three HIV(+) heterosexual men, and five HIV(+) homosexual men were also analyzed.
  
  
  
  We estimated the total number of kisspeptin-immunoreactive neurons within the infundibular nucleus.
  
  
  
  Quantitative analysis confirmed that the human infundibular kisspeptin system exhibits a female-dominant sex difference. The number of kisspeptin neurons is significantly greater in the infant/prepubertal and elderly periods compared with the adult period. Finally, in MTF transsexuals, but not homosexual men, a female-typical kisspeptin expression was observed.
  
  
  
  These findings suggest that infundibular kisspeptin neurons are sensitive to circulating sex steroid hormones throughout life and that the sex reversal observed in MTF transsexuals might reflect, at least partially, an atypical brain sexual differentiation.
authors.affiliation: Groupe Interdisciplinaire de Génoprotéomique Appliquée Neurosciences (M.T., J.B.), University of Liège, 4000 Liège, Belgium; Neuroendocrinology Laboratory (A.S.S., J.B.) and Neuropsychiatric Disorder Laboratory (D.F.S.), Netherlands Institute for Neuroscience, 1105 BA Amsterdam, The Netherlands; and Department of Investigative Medicine (M.A.G., S.R.B.), Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom.
authors.forename: Melanie
authors.initials: M
authors.lastname: Taziaux
authors.affiliation: Groupe Interdisciplinaire de Génoprotéomique Appliquée Neurosciences (M.T., J.B.), University of Liège, 4000 Liège, Belgium; Neuroendocrinology Laboratory (A.S.S., J.B.) and Neuropsychiatric Disorder Laboratory (D.F.S.), Netherlands Institute for Neuroscience, 1105 BA Amsterdam, The Netherlands; and Department of Investigative Medicine (M.A.G., S.R.B.), Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom.
authors.forename: Annemieke S
authors.initials: AS
authors.lastname: Staphorsius
authors.affiliation: Groupe Interdisciplinaire de Génoprotéomique Appliquée Neurosciences (M.T., J.B.), University of Liège, 4000 Liège, Belgium; Neuroendocrinology Laboratory (A.S.S., J.B.) and Neuropsychiatric Disorder Laboratory (D.F.S.), Netherlands Institute for Neuroscience, 1105 BA Amsterdam, The Netherlands; and Department of Investigative Medicine (M.A.G., S.R.B.), Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Ghatei
authors.affiliation: Groupe Interdisciplinaire de Génoprotéomique Appliquée Neurosciences (M.T., J.B.), University of Liège, 4000 Liège, Belgium; Neuroendocrinology Laboratory (A.S.S., J.B.) and Neuropsychiatric Disorder Laboratory (D.F.S.), Netherlands Institute for Neuroscience, 1105 BA Amsterdam, The Netherlands; and Department of Investigative Medicine (M.A.G., S.R.B.), Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
authors.affiliation: Groupe Interdisciplinaire de Génoprotéomique Appliquée Neurosciences (M.T., J.B.), University of Liège, 4000 Liège, Belgium; Neuroendocrinology Laboratory (A.S.S., J.B.) and Neuropsychiatric Disorder Laboratory (D.F.S.), Netherlands Institute for Neuroscience, 1105 BA Amsterdam, The Netherlands; and Department of Investigative Medicine (M.A.G., S.R.B.), Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom.
authors.forename: Dick F
authors.initials: DF
authors.lastname: Swaab
authors.affiliation: Groupe Interdisciplinaire de Génoprotéomique Appliquée Neurosciences (M.T., J.B.), University of Liège, 4000 Liège, Belgium; Neuroendocrinology Laboratory (A.S.S., J.B.) and Neuropsychiatric Disorder Laboratory (D.F.S.), Netherlands Institute for Neuroscience, 1105 BA Amsterdam, The Netherlands; and Department of Investigative Medicine (M.A.G., S.R.B.), Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom.
authors.forename: Julie
authors.initials: J
authors.lastname: Bakker
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D002648:Child; D005260:Female; D005783:Gender Identity; D006801:Humans; D007223:Infant; D059648:Kisspeptins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics; D019529:Sexuality / Q000502:physiology*; D014189:Transsexualism / Q000378:metabolism*; D055815:Young Adult
chemical_list: D059648:Kisspeptins