Thyrotropin-Releasing Hormone (TRH), Free Acid (TRH-OH) is a physiological metabolite of Thyrotropin-Releasing Hormone. In Vitro: TRH degradation products have been shown to be associated with a number of endocrine- and central nervous system-related biological functions. TRH (pGlu-His-Pro-NH2) can be enzymatically degraded in plasma and brain tissue to yield TRH-OH. TRH and hGHRH stimulate the release of [³H]GH into the culture medium to 435 and 464%, respectively, when compared to the control, but TRH-OH has no effect^[1]. TRH-OH, produced after cleavage of the C-terminal amide group by a specific proline endopeptidase, is one of the most stable derivatives of TRH and is found at high levels in numerous brain regions. TRH-OH inhibits Na⁺ channel activity in mammalian septal neurons. In about 60% of the cells tested, TRH-OH at concentrations between 0.01 and 2.5 μM produces a dose-dependent reversible attenuation of Na+ currents. With 2 μM TRH-OH, peak Na⁺ current amplitude is reduced by 20-50%^[2].