Endocrine Abstracts

The major source of neurokinin B (NKB), a peptide of the tachykinin family, is the placenta. Little is known of the regulation of NKB or its preferred hypertensive-inducing receptor, NK3, during pregnancy, nor, the mechanisms leading to elevated NKB associated with pre-eclampsia (PE) during the third trimester. Using the pregnant rat we have looked at the changes in NKB and NK3 expression using real time PCR between day 16 and 21 of gestation in the placenta, brain and different peripheral tissues. Significant down-regulation of NKB (3 fold) and NK3 (47 fold, virtually switched off) was found in placenta approaching term. In rat brain there was no change in NKB or NK3 expression, but in peripheral tissues, the heart, liver and kidney there was a trend towards down-regulation between 1.4-1.7 and 1.7-2.5 fold, respectively. In humans, comparison of NKB and NK3 expression between normal and PE placenta at term demonstrated significantly higher amounts (1.6 fold) of NKB mRNA in PE, while NK3 remained unchanged. It has been proposed that such elevated levels of NKB in PE are the response to hypoperfusion and an ischaemic placenta. We tested this by culturing placental cytotrophoblasts under hypoxic conditions (2%O2), however, this resulted in a significant down-regulation (1.8 fold) of NKB, while NK3 remained unchanged. In conclusion, NKB and NK3 expression are down-regulated during the third trimester in the pregnant rat model. This effect was significant in the placenta compared to the peripheral tissues and may suggest the placenta is the source of a circulating down-regulating factor. NKB expression was found to be higher in PE at term, but was not up-regulated by hypoxia. It is plausible that elevated NKB levels in PE are caused by the disruption/failure to down-regulate the NKB/NK3 system during the third trimester. Local Ethical approval was obtained for human placenta.