DEVELOPMENTAL REGULATION OF THE PLACENTAL PROLACTIN-GROWTH HORMONE GENE FAMILIES IN THE PLACENTA
Prolactin (PRL) and growth hormone (GH) are structurally similar hormones that evolved from a common ancestral gene and have important roles in regulating reproduction and metabolism. There are now known to be multiple variants of the genes encoding these and other PRL/GH-like hormones, such as the placental lactogens, growth hormone variants and prolactin-like proteins, which are expressed in the anterior pituitary and placenta in a tissue, cell and species specific manner. During pregnancy, the placental production of these hormones is believed to control maternal resource allocation both to the fetus by metabolic actions in the mother and to the neonate through effect on mammary development. However, little is known about the regulation of the placental expression of these gene families either developmentally or in response to altered environmental conditions during pregnancy. The aim of this project is to compare the developmental and environmental regulation of the PRL/GH gene families in two species, the mouse and the sheep, in which pregnancy makes very different metabolic demands on the mother. In mice, the gravid uterus accounts for 30% of maternal mass by term whereas in sheep this value is only 10%. Using RT-PCR, in situ hybridisation, immunohistochemistry, the specific objective of the project are to answer the following two questions in placenta collected at specific gestational ages in the two species.
- How does placental expression of the PRL/GH gene families alter as fetal metabolic demands increase with increasing growth and proximity to the onset of lactation?
- How does placental expression of the PRL/GH gene families alter in response to challenges common in compromised pregnancies such as intrauterine growth restriction, hypoxia, overexposure to glucocorticoid stress hormones.
These placental measurements will be related to circulating hormone concentrations and to maternal biometry and metabolic status. Together, these studies will determine the role of the placenta in regulating the maternal metabolic adaptation to pregnancy, particularly in late gestation when the fetal and maternal metabolic demands are most finely balanced. The results will have clinical implications for compromised human pregnancies and, more fundamentally, for are basic understanding of conceptus-maternal signalling during pregnancy.