title: Sex differences in the neurokinin B system in the human infundibular nucleus.
abstract: BACKGROUND
  The recent report that loss-of-function mutations in either the gene encoding neurokinin B (NKB) or its receptor (NK3R) produce gonadotropin deficiencies in humans strongly points to NKB as a key regulator of GnRH release.
  
  
  OBJECTIVE
  We used NKB immunohistochemistry on postmortem human brain tissue to determine: 1) whether the human NKB system in the infundibular nucleus (INF) is sexually dimorphic; 2) at what stage in development the infundibular NKB system would diverge between men and women; 3) whether this putative structural difference is reversed in male-to-female (MtF) transsexual people; and 4) whether menopause is accompanied by changes in infundibular NKB immunoreactivity.
  
  
  METHODS
  NKB immunohistochemical staining was performed on postmortem hypothalamus material of both sexes from the infant/pubertal period into the elderly period and from MtF transsexuals.
  
  
  RESULTS
  Quantitative analysis demonstrated that the human NKB system exhibits a robust female-dominant sexual dimorphism in the INF. During the first years after birth, both sexes displayed a moderate and equivalent level of NKB immunoreactivity in the INF. The adult features emerged progressively around puberty until adulthood, where the female-dominant sex difference appeared and continued into old age. In MtF transsexuals, a female-typical NKB immunoreactivity was observed. Finally, in postmenopausal women, there was a significant increase in NKB immunoreactivity compared to premenopausal women.
  
  
  CONCLUSIONS
  Our results indicate that certain sex differences do not emerge until adulthood when activated by sex steroid hormones and the likely involvement of the human infundibular NKB system in the negative and positive feedback of estrogen on GnRH secretion.
authors.affiliation: Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Neuroendocrinology Laboratory, 1105 BA Amsterdam, The Netherlands. mtaziaux@ulg.ac.be
authors.forename: Melanie
authors.initials: M
authors.lastname: Taziaux
authors.forename: Dick F
authors.initials: DF
authors.lastname: Swaab
authors.forename: Julie
authors.initials: J
authors.lastname: Bakker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology; D001111:Arcuate Nucleus of Hypothalamus / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D001344:Autopsy; D001923:Brain Chemistry; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D015287:Neurokinin B / Q000032:analysis / Q000378:metabolism*; D018042:Receptors, Neurokinin-3 / Q000032:analysis / Q000378:metabolism; D012727:Sex Characteristics; D014189:Transsexualism / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D018042:Receptors, Neurokinin-3; D015287:Neurokinin B