Dartois E, Bouton M M
Centre de Recherches Roussel-Uclaf, Romainville, France.
J Steroid Biochem. 1988;30(1-6):333-6. doi: 10.1016/0022-4731(88)90118-5.
In rat pituitary cells in primary culture glucocorticoids specifically inhibit PGE2 and ACTH secretions induced by TPA, a potent phorbol ester derivative (triamcinolone acetonide greater than dexamethasone greater than cortisol greater than or equal to corticosterone). However, while PGE2 secretion can be inhibited up to 80%, ACTH secretion can only be inhibited up to 40%. Similar inhibitory effects are observed with mepacrine, an inhibitor of phospholipase A2 (PLA2). Glucocorticoids having also been described as PLA2-inhibitors, their inhibitory effect on TPA-induced secretions could thus be related to their anti-PLA2 activity. Their inhibitory effect on PLA2 has been attributed to their ability to induce the synthesis of lipocortin, the activity of which could be regulated by activation of kinase C or EGF-receptor kinase. Since in our model, EGF-induced PGE2 secretion is also inhibited by dexamethasone, these results suggest that a lipocortin-like protein could be present in pituitary cells and involved in the effect of TPA and EGF on PGE2, and, at least partly, on ACTH release.
在原代培养的大鼠垂体细胞中，糖皮质激素可特异性抑制由佛波酯（一种有效的佛波醇酯衍生物，曲安奈德＞地塞米松＞皮质醇≥皮质酮）诱导的前列腺素E2（PGE2）和促肾上腺皮质激素（ACTH）的分泌。然而，虽然PGE2分泌最多可被抑制80%，但ACTH分泌最多只能被抑制40%。磷脂酶A2（PLA2）抑制剂米帕林也有类似的抑制作用。糖皮质激素也被描述为PLA2抑制剂，因此它们对佛波酯诱导的分泌的抑制作用可能与其抗PLA2活性有关。它们对PLA2的抑制作用归因于它们诱导脂皮质素合成的能力，其活性可通过蛋白激酶C或表皮生长因子（EGF）受体激酶的激活来调节。由于在我们的模型中，地塞米松也能抑制EGF诱导的PGE2分泌，这些结果表明垂体细胞中可能存在一种脂皮质素样蛋白，它参与了佛波酯和EGF对PGE2的作用，并且至少部分参与了对ACTH释放的作用。
