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Title: Progesterone control of human endometrial cells
Author: Dunn, C. L.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2003
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The present study has explored the factors involved in decidualisation using primary human ESC cultures. Quantitative real-time PCR (Q RT-PCR) and Enzyme-linked Immunoabsorbant Assays (ELISA) have been used to investigate effective in vitro stimuli of decidualisation. A combination of treatment with a progestin and either 8-Bromo cAMP or PGE2 was capable of stimulating decidualisation in ESC cultures as determined by increases in two markers of this process, prolactin and insulin-like growth factor-binding protein-1 (IGFBP-1). Further analysis has revealed the changes taking place within the PGE2 pathway in decidualising ESCs, including an upregulation in the EP2 prostaglandin receptor messenger RNA (mRNA) upon treatment with 8-Bromo cAMP plus a progestin. The results presented here have demonstrated a rise in IL-15 mRNA levels in parallel with in vitro decidualisation. It appears that both progesterone and the intracellular messenger, cAMP, are involved in decidualisation and IL-15 expression. IL-15 secretion from the cells is shown to be IFN-γ dependent. The expression of IL-15 and interferon-γ (IFN-γ) mRNA across the menstrual cycle has been established. Immunohistochemistry was used to determine IL-15 expression during stimulated early pregnancy compared with normal luteal controls and has shown that secretions of the CL, including progesterone and/or relaxin, have the ability to increase IL-15 expression in vivo. Primary cultures of human uNK and peripheral blood NK cells have been used for studying the T helper 2-type cytokine IL-10 which is believed important for the support for early pregnancy. In response to PGE2 treatment, uNK cells expressed and secreted raised levels of IL-10, an anti-informmatory cytokine. Further investigation into the interactions between the convergence of the cAMP and progesterone intracellular pathways and their receptors would be important in clarifying the exact mechanisms controlling ESC decidualisation and IL-15 regulation. The interactions between ESCs and uNK cells need to be clarified further to assess the roles uNK cells in reproductive processes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available