[Effects of progestins on human endometrium in vitro]

In order to obtain a better evaluation of the epithelial proliferation of the human endometrium, we developed an "in vitro" model to quantify the effects of hormonal treatments, as an "hormonogram". We particularly aimed to evaluate the effects of steroids used in the replacement hormone therapy during menopausis in the view of predicting and preventing the development of precancerous lesions of the endometrium. This study has evaluated the effects of different progestins currently used in hormone therapy, progesterone, medroxy-progesterone acetate (MPA), nomegestrol acetate (TX), norethindrone acetate (NOR) on human proliferative endometrium explant culture, using two means: prostaglandin F2 alpha (PGF2 alpha) output in medium culture, and immunoexpression of estradiol receptor (ER), progesterone receptor (PR) and proliferative antigen Ki67 in tissue. After culture, quantitative studies on ER or PR immunoexpression could be assessed by image analysis procedure in contrast to Ki67 immunoexpression too weak low in non tumorous endometrium to be quantified. PGF2 alpha output, was decreased by progesterone, TX and MPA in both proliferative endometrium subtypes. With regards to receptor immunoexpression, progesterone only decreased PR expression in proliferative endometrium. PR immunoexpression in stromal cells was decreased by all progestins in homogeneous proliferative endometrium explants. TX decreased PR and ER expression in glands and stroma of homogeneous proliferative endometrium. MPA exhibited similar effects but only on heterogeneous proliferative endometrium. In brief, our results show that in vitro progestative treatment on endometrium reduced PGF2 alpha output and decreased PR and/or ER immunoexpression, although the in vitro effects of each progestin were not similar and varied with the endometrium subtype (proliferative homogeneous or heterogeneous). This study opens new fields of research particularly to investigate the endometrial proliferative activity using explant culture.