Abstract

BackgroundProgesterone plays an important role in the proliferation and differentiation of human endometrial cells (hECs). Large-dose treatment with progesterone has been used for treatment of endometrial proliferative disorders. However, the mechanisms behind remain unknown.MethodsTo investigate the role of cyclin B1 in proliferation and differentiation of hECs in menstrual cycle, the expression of cyclin B1 throughout the menstrual cycle was evaluated in hECs. To determine the effects of progesterone on the proliferation, cell cycle progression and apoptosis of hECs and to test if cyclin B1 is involved in these effects, progesterone and/or Alsterpaullone (Alp, a specific inhibitor of Cyclin B1/Cdc2) were added to primary hECs. Cellular proliferation was evaluated with MTT test, cell cycle with propidium iodide (PI) staining and flow cytometry, apoptosis with FITC-Annexin V and the expression of cyclin B1 with Western blotting.ResultsThe expression level of cyclin B1 in secretory endometria was significantly lower than in proliferative endometria (p < 0.01). Progesterone significantly inhibited the growth of hECs in a concentration-dependent manner (P < 0.01). The treatment with progesterone significantly decreased the expression of cyclin B1, increased the proportions of cell in G2/M phase, and apoptotic cells (P < 0.05 for all). The presence of Alp significantly enhanced the effects of progesterone on cyclin B1 down-regulation, G2/M cell cycle arrest and induction of apoptosis (P < 0.01 for all).ConclusionOur findings suggest that cyclin B1 is a critical factor in proliferation and differentiation of hECs. Progesterone may inhibit cell proliferation, mediate G2/M cell cycle arrest and induce apoptosis in hECs via down-regulating Cyclin B1.

Highlights

  • Progesterone plays an important role in the proliferation and differentiation of human endometrial cells

  • As the detection of significantly down-regulated expression of cyclin B1 in secretory endometria strongly suggests that cyclin B1 plays an important role in proliferation and differentiation of human endometrial cells (hECs) under steroids regulation, we examined the effects of progesterone on the proliferation, cell cycle progression and apoptosis of hECs and tested if cyclin B1 is involved in these effects

  • The result showed that the relative expression of cyclin B1 in human endometrium at the secretory phase is significantly lower than the proliferative phase (P < 0.01) (Figure 1)

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Summary

Introduction

Progesterone plays an important role in the proliferation and differentiation of human endometrial cells (hECs). Estrogen stimulates proliferation of both glandular epithelial cells and stromal cells, whereas progesterone prevents this effect and induces secretory changes in glandular epithelial cells and decidual changes in stromal cells[2]. The balance between these two hormones plays important roles in regulation of the menstrual cycle, ovulation, implantation and pregnancy. Recent clinical studies have raised concern about an increased risk of cardiovascular disease or breast cancer[8] It highlights the importance of insights from molecular biology of progesterone action on endometrium which may provide us with more precise markers for progesterone actions and help avoid side-effects and lead to new therapeutic proposal

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