Studies on the gonadotropin-releasing activity of thymulin: Changes with age

We assessed the ability of thymulin, a zinc-dependent nonapeptide produced by the thymic epithelial cells, to influence the release of luteinizing hor mone (LH) and follicle-stimulating hormone (FSH) from dispersed anterior pi tuitary (AP) cells from young, adult, and senescent female rats. Perifusion of young and senescent AP cells with thymulin doses of 10(-6) to 10(-5) M gave a significant stimulatory response for LH hut not FSH. Gonadotropin re lease was always Lower in the senescent cells. AP cells from both ape group s incubated with 10(-8) to 10(-3) hi thymulin showed a time- and dose-depen dent response for both gonadotropins, with a maximal stimulation at 10(-7) M. Preincubation of thymulin with an antithymulin serum completely quenched the secretagogue activity of the hormone. Coincubation of thymulin with th e secretagogue gonadotropin-releasing hormone (GnRH) revealed a synergistic effect on LH release and an additive effect on the release of FSH. The cal cium chelator EGTA blocked the gonadotropin-releasing activity of thymulin in AP cells. The cAMP enhancers, caffeine, NaF, and forskolin significantly increased the thymulin-stimulated release of gonadotropins. The inositol p hosphate enhancer LICL potentiated the action of thymulin on gonadotropins. It is concluded that the gonadotropin-releasing activity documented here f or thymulin is an age- and receptor-dependent effect mediated in part hy ca lcium, cAMP, and inositol phosphates.