Growth hormone-releasing activity of thymulin on pituitary somatotropes isage dependent

Thymulin is a Zn-bound nonapeptide produced by the thymic epithelial cells (IEC) whose secretion is modulated by growth hormone (GH), among others. We assessed the ability of thymulin to influence the release of GH from dispe rsed anterior pituitary (AP) cells from young, middle-aged and senescent Sp rague-Dawley female rats. Perifused and incubated AP cells were used in dif ferent sets of experiments and GH release was measured by RIA. Perifusion o f 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 thymu lin showed a time- and dose-dependent response, the latter being bell-shape d with a maximum at 10(-7) M thymulin. Preincubation of thymulin with an an tithymulin serum completely quenched the secretagogue activity of the hormo ne; Coincubation of thymulin with GHRH revealed a semiadditive release of G H in young and middle-aged AP cells and an additive effect in senescent cel ls. 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 sign ificantly increased the thymulin-stimulated release of GH while trifluopera zine, a protein kinase C inhibitor, had no effect. The inositol phosphate e nhancer LiCl potentiated the action of thymulin on GH release. The data sug gest that the GH-releasing activity of thymulin is receptor-mediated and in volves calcium, cAMP and inositol phosphates. In addition, senescence appea rs to impair somatotrope responsiveness to thymulin.