Endometrial Intracrinology--generation of an estrogen-dominated microenvironment in the secretory phase of women

Abstract

Context: The human endometrium is a complex multicellular tissue subject to cyclical fluctuations in ovarian-derived steroid hormones. Fertile cycles are characterized by differentiation (decidualization) of endometrial stromal cells (ESC).

Objective: To determine the impact of human stromal cell decidualization on biosynthesis and secretion of estrogens.

Design: Primary cell culture was used. Cells were decidualized in vitro. Some cultures were treated with an aromatase inhibitor.

Setting: A University Research Institute.

Patients: Primary ESC were derived from women with normal menstrual cycles (n = 12). None of the women were receiving hormonal therapy or suffering from endometriosis.

Main outcome measurements: Expression of mRNA and protein encoded by the aromatase (CYP19A1) and 3-β-hydroxysteroid dehydrogenase (HSD3B1) genes was assessed. Aromatase activity was measured using a tritiated water assay; steroid metabolism was determined using thin layer chromatography. Estrone (E1) and estradiol (E2) in cell culture media were measured by ELISA.

Results: Decidualization induced a two-fold increase in aromatase mRNA. Aromatase protein was only detected in decidualized ESC. 3-β-Hydroxysteroid dehydrogenase protein was present in ESC both before and after decidualization; concentrations appeared unchanged. The existence of functional aromatase in decidualized ESC was confirmed; E1 and E2 were secreted into culture media in decidualized ESC and concentrations were reduced when cells were incubated with an aromatase inhibitor. Decidualization resulted in reduced metabolism of E2 and an increase in the ratio of E2:E1.

Conclusions: Decidualization is characterized by an increase in aromatase expression/activity favoring the generation of an E2-dominated estrogen microenvironment within the endometrial stroma.