Morgan R O, Chang J P, Catt K J
J Biol Chem. 1987 Jan 25;262(3):1166-71.
The hypothalamic neuropeptide gonadotropin-releasing hormone (GnRH) stimulates luteinizing hormone secretion via receptor-mediated activation of phosphoinositide hydrolysis to yield inositol phosphates and diacylglycerol. Application of anion-exchange high-performance liquid chromatography together with absorbance and radiochemical flow detection has enabled both the characterization and quantitative estimation of pituitary cell inositol phosphates and phosphoinositides. In cultured pituitary cells, GnRH caused a rapid and progressive rise in the formation of inositol 1,4,5-trisphosphate and of higher polyphosphoinositols corresponding to inositol tetrakisphosphate, pentakisphosphate, and hexakisphosphate. The inositol 1,4,5-trisphosphate formed during GnRH action was dephosphorylated predominantly via inositol 4-monophosphate rather than the expected metabolite, inositol 1-monophosphate. The catabolism of inositol 4-monophosphate, like that of inositol 1-monophosphate, was inhibited by lithium. For these reasons and because it was the major metabolite of [3H] inositol 1,4,5-trisphosphate in permeabilized gonadotrophs, inositol 4-monophosphate appears to represent a specific marker for ligand-stimulated inositol polyphosphate formation and metabolism. The marked and sustained elevations of inositol 4-monophosphate and inositol 1,4-bisphosphate in GnRH-stimulated gonadotrophs indicate that polyphosphoinositides rather than phosphatidylinositol are the preferred substrates of phospholipase C during GnRH action.
下丘脑神经肽促性腺激素释放激素（GnRH）通过受体介导的磷酸肌醇水解激活作用刺激促黄体生成素的分泌，从而产生肌醇磷酸酯和二酰基甘油。应用阴离子交换高效液相色谱法结合吸光度和放射化学流动检测，能够对垂体细胞的肌醇磷酸酯和磷酸肌醇进行表征和定量估计。在培养的垂体细胞中，GnRH导致肌醇1,4,5-三磷酸以及对应于肌醇四磷酸、五磷酸和六磷酸的高级多磷酸肌醇的形成迅速且逐步增加。GnRH作用过程中形成的肌醇1,4,5-三磷酸主要通过肌醇4-单磷酸而不是预期的代谢产物肌醇1-单磷酸去磷酸化。肌醇4-单磷酸的分解代谢，与肌醇1-单磷酸的分解代谢一样，受到锂的抑制。基于这些原因，并且由于它是通透的促性腺激素细胞中[3H]肌醇1,4,5-三磷酸的主要代谢产物，肌醇4-单磷酸似乎代表了配体刺激的肌醇多磷酸形成和代谢的特异性标志物。GnRH刺激的促性腺激素细胞中肌醇4-单磷酸和肌醇1,4-二磷酸的显著且持续升高表明，在GnRH作用期间，多磷酸肌醇而非磷脂酰肌醇是磷脂酶C的首选底物。
