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 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.
Brown
O A
OA
INIBIOLP-Histology B, School of Medicine, National University of La Plata, Argentina.
Sosa
Y E
YE
Dardenne
M
M
Pléau
J M
JM
Goya
R G
RG
D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology; D007295:Inositol Phosphates / Q000502:physiology; D007986:Luteinizing Hormone / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D013935:Thymic Factor, Circulating / Q000494:pharmacology / Q000502:physiology*
D002614:Chelating Agents; D007295:Inositol Phosphates; D007987:Gonadotropin-Releasing Hormone; D004533:Egtazic Acid; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013935:Thymic Factor, Circulating; D002118:Calcium