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Premature birth is a major cause of neonatal death and intellectual and other handicaps among the survivors. While neonatal intensive care has improved the survival of premature babies, there has been no reduction in the number of premature babies born, in fact the numbers are increasing. Our inability to reduce premature birth is partly related to our lack of knowledge of the physiological processes that lead to normal labour. As a result many of our drugs for women in premature labour are not ....Premature birth is a major cause of neonatal death and intellectual and other handicaps among the survivors. While neonatal intensive care has improved the survival of premature babies, there has been no reduction in the number of premature babies born, in fact the numbers are increasing. Our inability to reduce premature birth is partly related to our lack of knowledge of the physiological processes that lead to normal labour. As a result many of our drugs for women in premature labour are not very effective. We have recently identified a novel pathway that regulates the activity of the muscle cells that form the uterus. This project seeks to understand the biochemical processes that change a muscle cell so that it begins to contract actively at the end of pregnancy. Specifically the project will examine two proteins called HSP20 and HSP27. These proteins have recently been reported to play a critical role in the contraction and relaxation of smooth muscle cells in the heart and blood vessels. We have identified for the first time that these proteins are also present in the muscle of the human uterus. It is likely that they play a critical role in regulating the contractions of the uterus. By understanding this process better we may be able to design better treatments to prevent premature birth.Read moreRead less
Premature birth is a major cause of neonatal death and intellectual and other handicaps among the survivors. While neonatal intensive care has improved the survival of premature babies, there has been no reduction in the number of premature babies born, in fact the numbers are increasing. Our inability to reduce premature birth is partly related to our lack of knowledge of the physiological processes that lead to normal labour. As a result many of our drugs for women in premature labour are not ....Premature birth is a major cause of neonatal death and intellectual and other handicaps among the survivors. While neonatal intensive care has improved the survival of premature babies, there has been no reduction in the number of premature babies born, in fact the numbers are increasing. Our inability to reduce premature birth is partly related to our lack of knowledge of the physiological processes that lead to normal labour. As a result many of our drugs for women in premature labour are not very effective. Our work has shown that a hormone called corticotrophin releasing hormone (CRH) made in the placenta plays a critical role in determining the length of a pregnancy. We have measured the levels of this hormone in the blood of pregnant women and shown that it increases more rapidly than normal in women who deliver prematurely and more slowly than normal in women who deliver late. It acts as a kind of clock to determine the length of pregnancy. What is not known is how this hormone acts to bring on labour. What is particularly puzzling is that some of the actions of the CRH seem likely to cause the uterus to relax rather than to contract. We wish to test the idea that the rapidly rising levels of this hormone in late pregnancy cause changes in the uterus that stop the pathways to relaxation and lead to contraction. To perform these studies we will use small pieces of uterus donated with informed consent from women undergoing caesarean section. The results of these studies may allow us to design better ways of preventing premature birth and prevent many cases of cerebral palsy and intellectual handicap.Read moreRead less
This project will test if the ratio of the two different estrogens found in the blood of pregnant women is the critical factor in determining the onset of contractions in the uterus at labour. The studies will also determine the role of a newly discovered receptor for estrogens in allowing powerful contractions at labour. Results will allow development of new treatments to prevent premature birth that block the actions of estrogen at this new receptor or change the ratio of the two estrogens.
Regulation Of Progesterone Action In Human Parturition.
Funder
National Health and Medical Research Council
Funding Amount
$314,983.00
Summary
Premature birth is the leading cause of neonatal death and sickness, and numbers are increasing due to our ignorance of the biology of labour. Progesterone maintains pregnancy and its withdrawal results in birth, but how this is achieved in humans is unknown. This project will determine the molecular mechanisms by which progesterone action is regulated during the transition from pregnancy to birth. This data will guide new strategies to prevent premature birth.