Role of Changes in Progesterone Receptor Expression in the Triggering of Labour
Supervisor: Associate Professor Tamas Zakar
The maintenance of pregnancy requires adequate levels of the steroid hormone progesterone in the maternal circulation. In most mammalian species, progesterone levels fall in late gestation leading to the onset labour. In a few other mammals including all primates and the guinea pig, labour occurs in the presence of high progesterone levels, and the mechanism that triggers labour is unknown. Recent studies suggest that changes in the ratio of progesterone receptor isoforms determine the responsiveness of uterus to progesterone. These changes in expression may result in "functional" progesterone withdrawal and lead to labour onset. This project will test this possibility using pregnant guinea pigs as the experimental model. Gestational tissues will be obtained at advancing stages of late pregnancy, and progesterone receptor subtype mRNA and protein levels will be measured by real time RT-PCR and Western blotting, respectively. The cellular and sub-cellular localization of progesterone receptor isoforms will be determined by immunohistochemistry. We expectedly to detect changes in receptor subtype expression that would lead to decreased progesterone responsiveness with approaching labour. These studies will determine if drugs target specific progesterone receptor isoforms may be used to suppress premature labour.