ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2006) 11 P674

Transforming growth factor beta 1 and decidualisation of the human endometrium

NM Kane1, J Brosens3, HOD Critchley2 & RW Kelly1

1MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen’s Medical Research Institute, Edinburgh, United Kingdom; 2Reproductive and Developmental Sciences, Centre for Reproductive Biology, The Queen’s Medical Research Institute, Edinburgh, United Kingdom; 3Institute of Reproductive and Developmental Biology, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.

Introduction: Decidualisation of the endometrial stromal cell (ESC) is pivotal for successful implantation and is initiated in response to increasing progesterone levels. Transforming Growth Factor-β1 (TGFβ-1), a potent cytokine involved in many diverse cellular responses, is activated from the latent form in the mid-late secretory phase. Previous reports suggest that TGFβ-1 might oppose the action of progesterone, although no mechanism has been proposed. We have investigated whether TGFβ-1 may have an effect on progesterone receptor (PR) expression or function and inhibit decidualisation.

Methods: Quantitative real time PCR (TaqMan) and Promoter-Reporter studies were used to investigate the role of TGFβ-1 in mediating nuclear PR expression and the decidualisation markers, IGFBP-1 and Prolactin expression, within ESCs decidualised in vitro. ESCs were isolated from patients undergoing gynaecological procedures for benign indications. Institutional ethical approval and written informal consent were obtained.

Results: TGFβ-1 (10 ng/ml, 2 h) upregulated nuclear PR expression in decidualised ESCs 2-fold (P<0.001) (n=5) however, at 12 h, 24 h and 36 h this upregulation was not seen. At 72 hours the nuclear PR mRNA expression levels were significantly downregulated 2-fold (P<0.05) (n=5). Western blotting and immunocytochemistry validated protein expression. The Promoter-Reporter study demonstrated that TGFβ-1 does not interfere with the transactivation potential of PR, indicating that the TGFβ-1 effect on PR expression is due to a decrease in genomic PR. IGFBP-1 and Prolactin mRNA and protein levels are downregulated with addition of TGFβ-1 indicating that TGFβ-1 inhibits decidualisation.

Summary: We have shown that TGFβ-1 interacts with progesterone, via its receptor, and could inhibit the decidualisation process. These findings highlight the complexity of interactions controlling the hormonal responses of the endometrial stromal cell.

Article tools

My recent searches

No recent searches.