Endocrine Abstracts

The process of sexual differentiation has been defined by examining animal models and human conditions where errors of sexual development result in ambiguous genitalia. The study of transsexualism where the cognitive sexual phenotype is not concordant with the individual's physical and genetic phenotype has also been important.

The sex determining region of the Y chromosome controls male gonadal development by inducing SOX 9 which causes testicular differentiation and anti Mullerian hormone production. Transcriptional factors such as DMRT 1, M33, SF-1 and WT-1 are important in the development of the bipotential gonad and later testicular differentiation.

Testosterone production by the foetal testis continues male differentiation, supporting Wolffian duct development and inducing the production of anti Mullerian hormone causing regression of the Mullerian ducts. Lack of testosterone or androgen receptor defects (AIS) in an XY individual result in feminization of the genitalia. Dihydrotestosterone is the main androgen responsible for development of male external genitalia. Reduced 5 alpha reductase activity also leads to feminization of the external genitalia in males whilst in females, exposure to high androgen levels in utero (CAH) masculinizes the genitals.

In females lack of SRY allows granulosa cell differentiation in the gonadal mesoderm resulting in primordial follicles formation. The transcription factors WNT4 and DAX-1 are important in this process and abnormalities of their action result in XX sex reversal.

Sexual development of the brain is central to the expression of gender role and sexual behaviour. Differences in neuronal density and function in the hypothalamic nuclei important in reproduction and parental behaviour (BST INAH SCN) are seen between genders. In humans there are differences in the neuronal density and neuropeptide expressions in sexually dimorphic nuclei between heterosexual, homosexual and transgender individuals that suggest neuroanatomical factors may contribute to both sexual orientation and gender identity.