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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.
Published: June 2016
AI Article Synopsis
Article Abstract
Context: 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.
Objectives: 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.
Design And Setting: Postmortem hypothalamic tissues were collected by The Netherlands Brain Bank, and sections were stained for kisspeptin by immunohistochemistry.
Patients: 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.
Main Outcome Measure: We estimated the total number of kisspeptin-immunoreactive neurons within the infundibular nucleus.
Results: 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.
Conclusions: 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.
