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Progesterone is an ovarian steroid hormone which plays a very important part in the regulation of pregnancy-related changes. Progesterone functions by binding to its specific nuclear receptor, PR, which regulates defined genes in a ligand dependent manner. The aim of my thesis is to explore and elucidate some of the important mediators of progesterone action with regards to pregnancy-related mammary gland development and also uterine development. Knockout mouse models and comparative wild type mice were used in order to explore the expression patterns of specific genes of interest. Quantitative PCR using cDNA derived from mammary gland tissue was used to analyse the differences in gene expression of progesterone’s downstream target molecules. Established target genes such as RANKL, Wnt4 and Amphiregulin, TGF-β1, Sfrp2 and Mig6 were analysed to determine their mRNA expression levels in the late stages of pregnancy where growth and proliferation is at its most intense. Comparisons were then made between the mammary gland and the uterus, in order to assess the tissue specificity of progesterone function. The results clearly indicate how progesterone is able to mediate both proliferative and anti-proliferative signals to ensure normal structural development within both the mammary gland and the uterus. A novel target gene; BDNF; was shown to be strongly regulated by PR and was also analysed in terms of the proliferative target genes to determine what functional role it may have in the signalling pathways. The findings of this study will help to further understand the intricacies of progesterone dependent signalling in both normal and tumourigenic mammary gland development.
Walsh, Claire A. (Thesis), "Analysis of progesterone-regulated target genes in mammary gland and uterine development" (2009). Masters. Paper 48.