Endocrine Abstracts

Tachykinins are a family of peptides comprising substance P, neurokinin B (NKB) and endokinin B (EKB) that are encoded on three separate genes, TAC1, 3 and 4, respectively. Traditionally classified as neurotransmitters the highest expression levels of EKB and NKB are found in the placenta, where, NKB has been implicated in pre-eclampsia (PE) and intrauterine growth restriction. We have conducted mRNA expression studies to look at the placental expression of each of the TAC genes in late rat pregnancy using quantitative PCR. We found each TAC gene to have its own unique expression profile. At day 21 (just before birth), TAC1 levels increased significantly (10.4-fold) compared to those levels found at day 16. TAC3 levels significantly declined (2.9-fold) between day 16 and 21, whilst, there was only a tendency for a modest 1.4-fold increase in TAC4 expression between days 16 and 21. In human placenta, comparison of TAC expression between 1^st trimester and term showed only a slight increase in TAC1 and 4 expression and a 2 fold increase in TAC3 expression at term. However, for ethical reasons we could not obtain longitudinal placental samples throughout the 3^rd trimester. To determine whether proposed pathophysiological triggers of PE could be responsible for changes in human TAC expression, we analysed the effects of hypoxia (2% O₂) and oxidative stress (presence of peroxynitrite or xanthine/xanthine oxidase) in term placental cytotrophoblast cultures. During hypoxia, there was a significant 2.7-fold and 1.8 fold decrease in TAC1 and 3 expression levels, respectively with no difference in TAC4 expression. No significant changes in TAC expression were observed in cytotrophoblasts grown under conditions of oxidative stress. Overall, there are significant changes in the expression of each of the TAC genes during pregnancy that could be species-specific. Evaluation of PE triggers demonstrated no evidence that they were responsible for increasing TAC expression, although, expression of TAC3 and αTAC4 were found to be significantly higher in term PE placenta than controls. Ethical approval was obtained for placenta.