Androgen receptor expression in the cervix of androgen-treated female-to-male transsexuals: association with morphology and chain-specific keratin expression.

Long-term androgen treatment of female-to-male transsexuals is associated with morphological changes of the ectocervical epithelium. This study was designed to correlate the histological changes of the ectocervix to modulation of androgen receptor (AR) and keratin expression. We evaluated AR expression by immunohistochemistry using monoclonal antibody F39.4 specific for the N-terminal domain of the human AR. In the cervix of five of six transsexuals, the epithelium of the ectocervix displayed areas of increased cellularity lacking complete maturation into flattened squamous epithelial cells. This morphological change was associated with the acquisition of keratins 8 and 19 by all cell layers. In the normal ectocervix, these keratins are characteristic of the basal cell layer. The morphologically altered ectocervix of transsexuals displayed an intense AR expression in all cell layers, which contrasts with the selective, faint nuclear staining of the basal cells of the ectocervix of both premenopausal and postmenopausal women. Additionally, long-term androgen treatment led to consistently increased AR expression by the stromal cells of the endocervix and ectocervix. Our data imply that the morphological changes in the transsexual ectocervix reflect an androgen-mediated arrest of maturation. The observed increase in AR expression by the stromal cells of the ectocervix of androgen-treated transsexual females provides an example of androgen-mediated upregulation of AR expression in human tissues.