Notch ligand-dependent gene expression in human endometrial stromal cells.

The purpose of this study is to investigate the expression patterns and role of Notch signaling in human endometrial cells. Notch receptors, Notch 1-3 were expressed in both endometrial epithelial and stromal cells. Notch ligands, Jag1 and Dll4 and Notch target genes, Hes1 and Hey1 were predominantly expressed in endometrial epithelial cells and scarce in stromal cells.

Progestagenic effects of tibolone are target gene-specific in human endometrial cells.

Objectives: Tibolone (Tib) exhibits progestagenic activities in addition to its tissue-specific estrogenic activities. The purpose of the current study was to determine the progestagenic actions of Tib and its metabolites using target genes known to be regulated by progestins in human endometrial glandular and stromal cells.

Methods: Human endometrial glandular and stromal cells were isolated from endometrial tissue fragments and separately incubated with Tib and its metabolites.

Effects of tibolone on nuclear receptors in human endometrial cells.

Objective: Tibolone regulates estrogenic activity in a tissue-selective manner. The purpose of this study was to evaluate the effects of tibolone on the mRNA content of nuclear receptors, estrogen receptor-alpha and beta (ERalpha and ERbeta), progesterone receptor (PR), and androgen receptor (AR) in human endometrial stromal and glandular cells.

Study Design: Human endometrial stromal and glandular cells were isolated from endometrial tissue fragments and separately incubated with tibolone and its metabolites.

Ligand activated relaxin receptor increases the transcription of IGFBP-1 and prolactin in human decidual and endometrial stromal cells.

The aim of this study was to investigate relaxin (RLX) receptor-mediated gene activation in human endometrium. We determined the promoter activities of insulin-like growth factor binding protein-1 (IGFBP-1) and prolactin (PRL) and identified sequence(s) that mediate RLX activated transcription in human decidual cells and endometrial stromal cells. In human decidual cells, the promoter activity of IGFBP-1 was increased significantly in cells incubated with RLX.

Progesterone receptor (hPR) upregulates the fibronectin promoter activity in human decidual fibroblasts.

Previous studies have shown that progestin induces the production of fibronectin (FN) and its mRNA content in human endometrial stromal cells. The mechanism of the upregulation was unclear. In the present study, we provide evidence that hPR regulates the FN promoter activity mainly through the CRE/AP1 site located in the proximal region of the promoter in human decidual fibroblasts.

Hox proteins activate the IGFBP-1 promoter and suppress the function of hPR in human endometrial cells.

Previous studies have shown that progestin activates the transcription of IGFBP-1 (insulin-like growth factor binding protein-1). Four regions in the IGFBP-1 promotor have been identified to enhance the transcription. Two of the regions, located at -73 to -65 bp and -319 to -311 bp formed identical DNA-protein complexes with the nuclear extracts of endometrial stromal/decidual cells.

Progesterone receptor activates its promoter activity in human endometrial stromal cells.

Previous studies have shown that progestin increases the content of progesterone receptor (hPRA and hPRB) and the hPR mRNA during decidualization of human endometrial stromal cells suggesting that endogenous hPR enhances the transcription of the hPR gene. In the present study, we provide evidence that hPR regulates the promoter activity mediated through an active Sp1 site. In stromal cells treated with medroxyprogesterone acetate, the promoter activity was significantly increased when cells were co-transfected with hPR expression vector.

Endometrial cell specific gene activation during implantation and early pregnancy.

Human endometrium expresses numerous genes to achieve an optimal uterine environment for implantation and maintaining the pregnancy. In this review, we will summarize our previous observations on progestin regulated gene expression, estrogen metabolic enzymes, nitric oxide synthase, aromatase, IGF-I and II, IGFBP-1, prolactin and glycodelin. These genes are differentially activated in two types of endometrial cells during the menstrual cycle and early pregnancy.