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

• Published in: The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2000-04, Vol.55 (4), p.B170-B176
• Main Authors: Brown, O A, Sosa, Y E, Dardenne, M, Pléau, J M, Goya, R G
• Format: Article
• Language: English
• Subjects: Aging; Aging - physiology; Androgens; Animals; Calcium - physiology; Cell Line; Cells, Cultured; Chelating Agents - pharmacology; Dose-Response Relationship, Drug; Egtazic Acid - pharmacology; Female; Follicle Stimulating Hormone - metabolism; Gerontology; Gonadotropin-Releasing Hormone - pharmacology; Gonadotropin-Releasing Hormone - physiology; Hormones; Inositol Phosphates - physiology; Luteinizing Hormone - metabolism; Mice; Mice, Inbred BALB C; Pituitary Gland, Anterior - metabolism; Rats; Rats, Sprague-Dawley; Rats, Wistar; Signal Transduction - physiology; Thymic Factor, Circulating - pharmacology; Thymic Factor, Circulating - physiology
• ISSN: 1079-5006; 1758-535X
• DOI: 10.1093/gerona/55.4.B170

We assessed the ability of thymulin, a zinc-dependent nonapeptide produced by the thymic epithelial cells, to influence the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from dispersed anterior pituitary (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 but not FSH. Gonadotropin release was always lower in the senescent cells. AP cells from both age groups incubated with 10(-8) to 10(-3) M thymulin showed a time- and dose-dependent 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 the secretagogue gonadotropin-releasing hormone (GnRH) revealed a synergistic effect on LH release and an additive effect on the release of FSH. The calcium 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 phosphate enhancer LiCl potentiated the action of thymulin on gonadotropins. It is concluded that the gonadotropin-releasing activity documented here for thymulin is an age- and receptor-dependent effect mediated in part by calcium, cAMP, and inositol phosphates.