Brown O A, Sosa Y E, Dardenne M, Pléau J, Goya R G
INIBIOLP-Histology B, School of Medicine, National University of La Plata, Argentina.
Neuroendocrinology. 1999 Jan;69(1):20-7. doi: 10.1159/000054399.
Thymulin is a Zn-bound nonapeptide produced by the thymic epithelial cells (TEC) whose secretion is modulated by growth hormone (GH), among others. We assessed the ability of thymulin to influence the release of GH from dispersed anterior pituitary (AP) cells from young, middle-aged and senescent Sprague-Dawley female rats. Perifused and incubated AP cells were used in different sets of experiments and GH release was measured by RIA. Perifusion of young and senescent AP cells with thymulin doses, ranging from 10(-8) to 10(-5) M, gave a logarithmic dose-response pattern of GH. Supernatants from TEC lines also showed GH secretagogue activity. The GH release was always lower in the senescent cells. AP cells incubated with 10(-8)-10(-3) M thymulin showed a time- and dose-dependent response, the latter being bell-shaped with a maximum at 10(-7) M thymulin. Preincubation of thymulin with an antithymulin serum completely quenched the secretagogue activity of the hormone. Coincubation of thymulin with GHRH revealed a semiadditive release of GH in young and middle-aged AP cells and an additive effect in senescent cells. In middle-aged AP cells, the synthetic GH secretagogue GHRP-6 showed a synergistic effect with thymulin on GH release. The calcium chelator EGTA, but not the calcium ionophore A23187, blocked the GH-releasing activity of thymulin in AP cells. The cAMP enhancers, caffeine, NaF and forskolin significantly increased the thymulin-stimulated release of GH while trifluoperazine, a protein kinase C inhibitor, had no effect. The inositol phosphate enhancer LiCl potentiated the action of thymulin on GH release. The data suggest that the GH-releasing activity of thymulin is receptor-mediated and involves calcium, cAMP and inositol phosphates. In addition, senescence appears to impair somatotrope responsiveness to thymulin.
胸腺素是一种由胸腺上皮细胞（TEC）产生的锌结合九肽，其分泌受生长激素（GH）等多种因素调节。我们评估了胸腺素对幼年、中年和老年斯普拉格-道利雌性大鼠分散的垂体前叶（AP）细胞释放GH的影响能力。在不同组实验中使用了灌注和培养的AP细胞，并通过放射免疫分析法（RIA）测量GH释放。用10(-8)至10(-5) M的胸腺素剂量灌注幼年和老年AP细胞，呈现出GH的对数剂量反应模式。TEC系的上清液也显示出GH促分泌活性。老年细胞中的GH释放始终较低。用10(-8)-10(-3) M胸腺素培养的AP细胞表现出时间和剂量依赖性反应，后者呈钟形，在10(-7) M胸腺素时达到最大值。胸腺素与抗胸腺素血清预孵育完全消除了该激素的促分泌活性。胸腺素与生长激素释放激素（GHRH）共同孵育显示，在幼年和中年AP细胞中GH呈半加性释放，在老年细胞中呈加性效应。在中年AP细胞中，合成的GH促分泌剂GHRP-6与胸腺素对GH释放具有协同作用。钙螯合剂乙二醇双四乙酸（EGTA）而非钙离子载体A23187可阻断胸腺素在AP细胞中的GH释放活性。环磷酸腺苷（cAMP）增强剂咖啡因、氟化钠（NaF）和福斯可林显著增加了胸腺素刺激的GH释放，而蛋白激酶C抑制剂三氟拉嗪则无作用。肌醇磷酸增强剂氯化锂（LiCl）增强了胸腺素对GH释放的作用。数据表明，胸腺素的GH释放活性是受体介导的，涉及钙、cAMP和肌醇磷酸。此外，衰老似乎会损害生长激素细胞对胸腺素的反应性。
