Pitutitary hormone-releasing hormones which are synthesized in the hypothalamus of the mammalian brain are now known as TRH,LHRH,CRH,GHRH,and so on. Among them, low molecular weight peptides, TRH and LHRH show the structural similarities. Both peptides have pyroGlu as N-terminal amino acid, His, and amino acid amide as C-terminal. We have already cleared that there is pyrogrutamyl peptidase in rat brain and the protease makes cyclic peptide ; histidyl-proline diketopiperazine. This cyclic peptide is supposed to behave as a brain activating substance. Biological activities of the releasing-hormones which show many functions including brain activating ability might be due to the cyclic peptides.
Under the circumstances we synthesized four peptides which contain His, then succeeded in making antibodies which have specificities against each cyclic peptide. Using the antibodies we wanted to develop the microdetermination and immunohistochemical methods which can clear the peptide distribution in the brain. Besides those, using pituitary cell culture and western blotting methods, we wanted to know the pituitary hormonereleasing abilities of cyclic peptides. Two years was not enough for this project. We now need more time, and the possibility of cyclic peptides as brain activating substances needs the experiments using animals in vivo.
This project was planned among 4 members at first, but two members were tranferred and were not able to join this project. Only 2 members started this project (afterwards another joined). So, we now making haste.