Temporal regulation of endocrine gene expression - timing in living cells and tissues. (360G-Wellcome-091688_D_10_Z)

We aim to understand the dynamic regulation of pituitary hormone gene expression in living cells and tissues using valuable transgenic rat models generated over our previous period of funding. Using luciferase or destabilised fluorescent proteins to report promoter activity in real time, we will use pituitary cells and tissue slice preparations to understand the spatio-temporal patterns of gene expression, with 4-dimensional non-linear mathematical modelling approaches to test in what ways cells are transcriptionally coordinated in different circumstances, including fetal and neonatal development, responses to oestrogen, and lactotroph hyperplasia. The transgenic rat models we have generated have shown dramatic induction of human prolactin gene expression in extra-pituitary tissues after inflammatory stress. In addition to detailed assessment of endogenous prolactin gene expression in human tissues, we will use this to identify the pathways involved in prolactin's role in different types of inflammatory response.