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Studies on the Gonadotropin-Releasing Activity of Thymulin

Changes With Age

^a INIBIOLP-Histology B, School of Medicine, National University of La Plata, Argentina
^b CNRS URA 1461, Université Paris V, Hôpital Necker, France.

Rodolfo G. Goya, INIBIOLP, Facultad de Medicina, UNLP, CC 455, 1900 La Plata, Argentina E-mail: rgoya{at}netverk.com.ar.

Decision Editor: Jay Roberts, PhD

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.

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