Charli J L, Vargas M A, Cisneros M, de Gortari P, Baeza M A, Jasso P, Bourdais J, Peréz L, Uribe R M, Joseph-Bravo P
Departamento de Genética y Fisiología Molecular, Universidad Nacional Autónoma de México, Cuernavaca.
Neurobiology (Bp). 1998;6(1):45-57.
TRH (pGlu-His-ProNH2) inactivation in the brain and pituitary extracellular fluid is reviewed. While TRH could be eliminated by alternative mechanisms, i.e. uptake or internalization, modification, hydrolysis by broad specificity peptidases such as pyroglutamyl peptidase I and prolyl endopeptidase, evidence accumulates to support a specific neuroectopeptidase as the main mechanism responsible for its extracellular inactivation. Pyroglutamyl peptidase II (PPII; E.C. 3.4.19.6) is a narrow specificity zinc metallopeptidase hydrolyzing the pyroglutamyl-histidyl peptide bond of TRH. PPII is an integral membrane protein with a small intracellular domain, a transmembrane segment and a large extracellular domain that contains the catalytic site. It is therefore idealy situated to degrade TRH present in the extracellular space. PPII is highly enriched in brain, specifically present in neuronal cells. PPII inhibition enhances recovery of TRH released in vitro. In situ hybridization studies demonstrate that PPII mRNA colocalizes with TRH-receptor mRNA in various brain regions. However, the existence of exceptions suggest that alternative inactivation mechanisms for TRH may operate. PPII activity is regulated in various pharmacological or pathophysiological conditions which alter TRH transmission. It is also present in adenohypophysis, preferentially on lactotrophs, where its activity is stringently regulated by hormones and hypothalamic factors. PPII activity regulation may contribute to adjust TRH neural and hormonal transmissions.
本文综述了促甲状腺激素释放激素（TRH，pGlu-His-ProNH2）在脑和垂体细胞外液中的失活情况。虽然TRH可通过其他机制被清除，如摄取、内化、修饰以及被诸如焦谷氨酰肽酶I和脯氨酰内肽酶等广泛特异性肽酶水解，但越来越多的证据支持一种特定的神经外肽酶是其细胞外失活的主要机制。焦谷氨酰肽酶II（PPII；E.C. 3.4.19.6）是一种特异性较窄的锌金属肽酶，可水解TRH的焦谷氨酰-组氨酰肽键。PPII是一种整合膜蛋白，具有一个小的细胞内结构域、一个跨膜片段和一个包含催化位点的大的细胞外结构域。因此，它处于理想位置以降解细胞外空间中存在的TRH。PPII在脑中高度富集，特别存在于神经元细胞中。PPII抑制可增强体外释放的TRH的恢复。原位杂交研究表明，PPII mRNA在各个脑区与TRH受体mRNA共定位。然而，存在的例外情况表明TRH可能存在其他失活机制。PPII活性在改变TRH传递的各种药理或病理生理条件下受到调节。它也存在于腺垂体中，优先存在于催乳素细胞上，其活性受到激素和下丘脑因子的严格调节。PPII活性调节可能有助于调节TRH的神经和激素传递。
