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TRH analog administration increases endogenous TRH levels in the central nervous system
C Prasad1, S Eloby-Childress, T Iriuchijima
1Department of Medicine, Louisiana State University Medical Center, New Orleans.
Abstract:
Experiments were carried out to increase the endogenous levels of TRH in brain and spinal cord. After 7 days of continuous oral ingestion of TRH analogs (D-pGlu-Leu-ProNH2, pGlu-Leu-Pro, pGlu-Pro-ProNH2, or pGlu-Leu-pyrrolidide), spinal cord and brain levels of TRH were elevated, whereas the content of TRH metabolite, cyclo(His-Pro), was decreased. In addition, the TRH analogs inhibited in vitro metabolism of [3H-Pro]-TRH by brain and spinal cord extracts. Our data show that certain TRH analogs can elevate tissue levels of TRH by inhibiting its metabolism. Furthermore, because these analogs do not affect interaction between TRH and its receptor, the elevated TRH can effectively enhance TRH-related bioactivity.