Quantitative histomorphometric analysis of gonadal steroid receptor distribution in the normal human endometrium through the menstrual cycle

Abstract

The aim of this study was to test the hypothesis that the distribution of oestrogen receptor beta (ERbeta) and androgen receptor (AR) are related to cell proliferation or correlated with the expression of progesterone receptor (PR) or oestrogen receptor alpha (ERalpha) in the normal human endometrium. Immunohistochemical distribution of immunoreactive ERbeta in well-characterised menstrual cycle biopsy samples was lowest in proliferative endometrial glands, highest in early secretory phase glands and maintained at approximately 20% throughout the rest of the menstrual cycle and was closely correlated with stromal AR and stromal ERbeta expression. Stromal ERbeta was not significantly altered until the menstrual phase of the cycle and was not correlated with the expression of any other antigen in the stroma or endometrial glands except stromal AR. By contrast, glandular AR immunoreactivity was below 5% early in the cycle, increased during the secretory phase and showed strong expression just before menstruation. PR and Ki-67 expression showed strong positive correlations, indicating that PR may be a potent regulator of endometrial proliferation. These data suggest that glandular ERbeta expression is closely associated with a functional secretory role whereas glandular ERalpha and PR are associated with proliferation; glandular AR expression may be the switch required for menstruation.