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Endometriosis is a common gynecological disorder of unclear pathogenesis. We have established an in vitro model to investigate phenotypic similarities and differences between normal endometrial and endometriosis cells. Highly purified cultures of epithelial and stromal cells were isolated from normal endometrium and endometriosis implants. Morphological features as well as immunocytochemical markers confirm these isolates as epithelial and stromal cells. Potential hormone responsiveness was established by the documentation of estrogen receptor mRNA in epithelial and stromal cells isolated from both tissue types. Expression of this receptor protein was verified in stromal cells by competitive radioligand binding, revealing comparable receptor numbers and dissociation constants. CA-125 is selectively secreted in similar concentrations by epithelial cells isolated from both tissue types. PRL secretion is selectively exhibited by progestin-stimulated stromal cells from both tissue types. Our findings demonstrate that highly purified epithelial and stromal cells cultured from normal endometrial and endometriosis tissues express the same phenotypic and functional markers as their in vivo counterparts. These cultures provide useful models to identify endometriosis-specific cell products that contribute to the pathogenesis of this disorder.

We evaluated the insulin response to a standard oral glucose tolerance test (OGTT) and in vitro insulin binding to erythrocytes (RBC) in 26 women from 3 groups: Group NW, normal women (n = 11); Group DS, women (n = 9) with elevated serum DHEAS concentrations, greater than 400 micrograms/dl (greater than 10.84 mumol/L); and Group IR, women (n = 6) with elevated basal plasma insulin concentrations (IRI). There was a significant linear correlation between the area under the insulin response curve (IRI-AUC) and serum testosterone (T) (r = 0.78, p = 0.0001). Using stepwise multiple linear regression, IRI-AUC was characterized as a function of both serum T and DHEAS; positively with T and negatively with DHEAS. In vitro (n = 17), there was a positive correlation between RBC-insulin binding and serum DHEAS (r = 0.54, p = 0.029) and a negative correlation between RBC-binding and T (r = -0.57, p = 0.017). We conclude that DHEAS may enhance insulin binding and action and that DHEAS and T have divergent functional relationships with IRI. DHEAS and T may therefore exert opposing effects on insulin secretion and action.

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An in vitro model developed to compare human endometrial and endometriosis stromal cells was used to examine basal and stimulated expression of interleukin (IL-6). Stromal cells isolated from normal endometrium (NE) exhibited the lowest level of IL-6 secretion (84 pg/10(6) cells-48 h), whereas those cells isolated from endometriosis implants (EI) secreted the highest concentration of this inflammatory cytokine (46,284 pg/10(5) cells-48 h; P < 0.01). Eutopic endometrial stromal cells from women with endometriosis (EE) expressed an intermediate concentration of IL-6 (831 pg/10(6) cells-48 h). Stimulation of the various cultures with IL-1 beta dramatically augmented stromal cell production of IL-6. The mean concentrations of stimulated IL-6 secretion were 16,257, 37,800, and 264,290 pg/10(5) cells-48 h for NE, EE, and EI cells, respectively (P < 0.03). Exposure of the cell cultures to 10 nmol/L estradiol had little direct effect on IL-6 production. The results indicate that endometrial stromal cells isolated from tissues of women with and without endometriosis express IL-6 under basal and cytokine-stimulated conditions. Differential responsiveness among the three cell sources indicates that NE, EE, and EI cells have intrinsic quantitative differences in cytokine regulation.