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Male-to-Female Transsexuals Have Female Neuron Numbers in a Limbic Nucleus

Graduate School Neurosciences Amsterdam (F.P.M.K., J.-N.Z., C.W.P., M.A.H., D.F.S.), Netherlands Institute for Brain Research, 1105 AZ Amsterdam ZO, The Netherlands; Department of Endocrinology (L.J.G.G.), Free University Hospital, 1007 MB Amsterdam, The Netherlands; and Anhui Geriatric Institute (J.-N.Z.), The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032 China

Address all correspondence and requests for reprints to: Frank P. M. Kruijver, M.D., or Prof. Dick F. Swaab, M.D., Ph.D., Graduate School Neurosciences Amsterdam, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam ZO, The Netherlands. E-mail: F.Kruijver{at}nih.knaw.nl

Transsexuals experience themselves as being of the opposite sex, despite having the biological characteristics of one sex. A crucial question resulting from a previous brain study in male-to-female transsexuals was whether the reported difference according to gender identity in the central part of the bed nucleus of the stria terminalis (BSTc) was based on a neuronal difference in the BSTc itself or just a reflection of a difference in vasoactive intestinal polypeptide innervation from the amygdala, which was used as a marker. Therefore, we determined in 42 subjects the number of somatostatin-expressing neurons in the BSTc in relation to sex, sexual orientation, gender identity, and past or present hormonal status. Regardless of sexual orientation, men had almost twice as many somatostatin neurons as women (P < 0.006). The number of neurons in the BSTc of male-to-female transsexuals was similar to that of the females (P = 0.83). In contrast, the neuron number of a female-to-male transsexual was found to be in the male range. Hormone treatment or sex hormone level variations in adulthood did not seem to have influenced BSTc neuron numbers. The present findings of somatostatin neuronal sex differences in the BSTc and its sex reversal in the transsexual brain clearly support the paradigm that in transsexuals sexual differentiation of the brain and genitals may go into opposite directions and point to a neurobiological basis of gender identity disorder.

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