Endocrine Abstracts

Factors influencing gender during early development, i.e., the feeling to be male or female, are prenatal hormones and compounds that change the levels of these hormones, such as anticonvulsants. While an influence of genetic factors must be present, an influence of postnatal social factors has not been established. In rodents, masculinization of the brain in development is due to oestrogens that are formed by aromatization of testosterone. In sexual differentiation of the human brain direct effects of testosterone seem to be of primary importance as is clear e.g. from subjects with mutations in the androgen receptor, estrogen receptor or aromatase (Swaab, 2004).

We observed a reversal of the sex difference in the Bed Nucleus of the Stria terminalis (BSTc) of transsexuals. The size, type of innervation and neuron number agreed with their gender and not with their genetic sex (Zhou et al., 1995; Kruijver et al., 2000). The period of overt structural sexual differentiation of the human hypothalamus occurs between approximately four years of age and adulthood, thus much later than is generally presumed, although the late sexual differentiation may of course be based upon processes that have already been programmed in mid-pregnancy or during the neonatal period (Chung et al., 2002).

Chung, W.C., De Vries, G.J., Swaab, D.F. (2002) J. Neurosci. 22: 1027-1033.

Kruijver, F.P.M., Zhou, J.N., Pool, C.W., Hofman, M.A., Gooren, L.J.G., Swaab, D.F. (2000) J. Clin. Endocrinol. Metabol. 85: 2034-2041.

Swaab, D.F. - The Human Hypothalamus. Basic and Clinical Aspects. Part I. Nuclei of the Hypothalamus (2003). Part II: Neuropathology of the Hypothalamus and Adjacent Brain Structure (2004). Handbook of Clinical Neurology, Vol 79 and 80, Elsevier, Amsterdam.

Zhou, J.N., Hofman, M.A., Gooren, L.J.G., Swaab, D.F. (1995) Nature 378: 68-70.