Berglund H, Lindström P, Dhejne-Helmy C, Savic I. Male-to-female transsexuals show sex-atypical hypothalamus activation when smelling odorous steroids. Cereb Cortex. 2008 Aug;18(8):1900-8
One working hypothesis behind transsexuality is that the normal sex differentiation of certain hypothalamic networks is altered. We tested this hypothesis by investigating the pattern of cerebral activation in 12 nonhomosexual male-to-female transsexuals (MFTRs) when smelling 4,16-androstadien-3-one (AND) and estra-1,3,5(10),16-tetraen-3-ol (EST). These steroids are reported to activate the hypothalamic networks in a sex-differentiated way. Like in female controls the hypothalamus in MFTRs activated with AND, whereas smelling of EST engaged the amygdala and piriform cortex. Male controls, on the other hand, activated the hypothalamus with EST. However, when restricting the volume of interest to the hypothalamus activation was detected in MFTR also with EST, and explorative conjunctional analysis revealed that MFTR shared a hypothalamic cluster with women when smelling AND, and with men when smelling EST. Because the EST effect was limited, MFTR differed significantly only from male controls, and only for EST-AIR and EST-AND. These data suggest a pattern of activation away from the biological sex, occupying an intermediate position with predominantly female-like features. Because our MFTRs were nonhomosexual, the results are unlikely to be an effect of sexual practice. Instead, the data implicate that transsexuality may be associated with sex-atypical physiological responses in specific hypothalamic circuits, possibly as a consequence of a variant neuronal differentiation.
Note the last line of the abstract: “…physiological responses in specific hypothalamic circuits, possibly as a consequence of a variant neuronal differentiation.” The abstract and article attest to the detailed link between nature (e.g., prenatal genetically predisposed organization of the gonadotropin releasing hormone (GnRH) system), and nurture (e.g., its activation by sensory input from the social environment) via a well-detailed gene-cell-tissue-organ-organ system pathway. Related publications by this group date back 7 years, and the neuroscience dates back much further. For example, Kohl JV, Atzmueller M, Fink B, Grammer K.Human pheromones: integrating neuroendocrinology and ethology. Neuro Endocrinol Lett. 2001 Oct;22(5):309-21. Review – was published before works from this group became available.
