Immunohistochemical Analysis of Human Uterine Estrogen and Progesterone Receptors Throughout the Menstrual Cycle*

Abstract

Estrogen receptors (ER) and progesterone receptors (PgR) were studied immunohistochemically using specific antireceptor monoclonal antibodies in uterine tissue samples from 33 women in various stages of the menstrual cycle. Immunohistochemical localization was quantified as to intensity of staining and tissue distribution in glandular epithelium, stroma, and myometrium, and the results were compared with those of standard ligand binding assays. In all samples ER and PgR localized within the nuclei of target cells. The maximal concentrations of ER and PgR occurred in the mid- to late proliferative phase of the menstrual cycle. ER content declined throughout the secretory phase. In contrast, PgR content underwent unexpectedly complex and dyssynchronous fluctuations during the secretory phase of the menstrual cycle. Specifically, the glandular epithelium had diminished PgR content, while the stroma and myometrium maintained a significant PgR content. PgR and perhaps ER are not concordant in different cell types within the uterus. Segregation of function through alteration of receptor content may be an important mechanism in steroid-dependent growth and differentiation of target tissues.

Influence of menstrual cycle, parity and oral contraceptive use on steroid hormone receptors in normal breast

“…The decrease in OR positive cases in the second half of the menstrual cycle is the same as the endometrium (Press et al, 1984;Lessey et al, 1988) and is consistent with the accepted dogma of OR down-regulation as a consequence of progesterone action. The present study further supports this from observations in OC cycle, where there is a striking decrease in detection with use, presumably on account of downregulation by exogenous progestins.…”

“…In part, the controversy reflects the difference in data derived from tissues obtained ex vivo from those derived from cell culture and from xenografts in nude mice, but another factor has been the assumption of similarity in the steroidal regulation of breast and endometrial epithelia. While a clear picture of oestrogen receptor and progesterone receptor regulation exists for endometrium (Lessey et al, 1988), the same is not true for breast. Oestrogen and progesterone receptors (OR and PR) are both present in normal human breast epithelium (Petersen et al, 1987;Jacquemier et al, 1990;Joyeux et al, 1990;Williams et al, 1991) but with lack of agreement between authors as to differences across the cycle or consistency within it.…”

Prognostic significance of erythropoietin expression in human endometrial carcinoma

“…This variability is related to the known effects of estrogen and progesterone on steroid hormone receptor expression. 22 Although steroids control endometrial function, paracrine and autocrine growth factor/cytokine signals are now viewed as key mediators of reproductive function. It has been suggested that neovascularization in normal endometrial tissue is indirectly modulated by ovarian steroids via the production of locally active angiogenic factors, such as vascular endothelial growth factor.…”

Alteration of maternal Hoxa10 expression by in vivo gene transfection affects implantation

“…Endometrial glandular growth is estrogen dependent, yet glandular estrogen receptors are downregulated and undetectable at the time of implantation. 21 Inductive stromal-epithelial interactions regulate endometrial growth and differentiation leading to endometrial receptivity. 22 Estrogen presumably stimulates endometrial glandular development via a paracrine mechanism acting through the stromal estrogen receptor.…”