On 5 October at 15:15 Indrek Teino will defend his doctoral thesis in cell biology “Studies on aryl hydrocarbon receptor in the mouse granulosa cell model” .
Professor Toivo Maimets, Institute of Molecular and Cell Biology, University of Tartu
Professor Jason Matthews, University of Oslo (Norway)
Environmental chemicals, including dioxins, affect the homeostasis of organism resulting in cancer and disturbances in the immune and reproductive system. Many of these chemicals act as ligands for aryl hydrocarbon receptor (AHR). Upon ligand binding, AHR translocates to the nucleus and modulates the expression of a variety of genes. Among these are genes responsible for the degradation of AHR ligands, but also genes necessary for normal functioning of cells. Several publications have shown high AHR expression and activity in cancers. Thus, AHR is a promising target in cancer research. However, the majority of attention has been focused on its activity modulation and the mechanisms governing AHR expression have stayed rather unclear. The role of AHR in reproduction is mainly associated with its positive effect on follicle stimulating hormone receptor (Fshr) and aromatase. These two genes are crucial for the proper functioning of granulosa cells, which support the maturation and ovulation of oocyte. In addition, it has been shown that Ahr expression fluctuates during reproductive cycle.
The aim of this thesis was to characterise the control of Ahr expression in mouse ovarian granulosa cells and to clarify by which mechanisms Ahr influences Fshr expression. It was uncovered that Ahr is upregulated via transient silencing of protein kinase A (PKA) signalling during maturation of granulosa cells. Following induction of ovulation, in turn, Ahr is silenced by PKA pathway. Lastly, a novel binding site for Ahr was ascertained by which Ahr regulates Fshr expression.