REDUCED ABILITY OF HYPOTHALAMIC AND PITUITARY EXTRACTS FROM OLD MICE TO STIMULATE THYMULIN SECRETION IN-VITRO

There is substantial evidence that growth hormone (GH) is particularly important in the control of the age-related decline of thymus functio n. It was therefore of interest: (a) to assess the overall capacity of tissue extracts from mediobasal hypothalamus (MBH), anterior pituitar y (AP) and testis, obtained from young (3 months, Y-c), middle-aged (1 3 months, MA(c)) and old (18 months, O-c) intact C57BL/6 mice to stimu late in vitro the release of thymulin, a Zn-bound immunoregulatory thy mic peptide, from pure cultures of mouse thymic epithelial cells (TEC) ; (b) to perform the same evaluation utilizing MBH, AP and testicular extracts from mice of the same age-range but treated for 45 days with a sc dose of ovine GH (2 mu g/g body wt) known to stimulate thymulin s ecretion in vivo. Pituitary hormones were measured by heterologous rat RIAs, whereas thymulin release was estimated by a rosette assay. Untr eated animals showed a significant age-dependent increase in the AP co ntent of follicle stimulating hormone but not in other AP hormones. In both control and treated animals, pituitary GH content decreased sign ificantly with age. MBH extracts from C57BL/6 males evidenced thymulin -releasing activity on mouse TEC lines. This activity was maximal in t he MBH from young animals and declined with the age of the MBH donors. The thymulin-releasing activity of MBHs from GH-treated mice was high er than that of the control animals and showed a less pronounced decli ne with age. AP extracts from the same animals showed a higher thymuli n-releasing activity than did MBH preparations. This activity showed a progressive age-associated reduction in the APs from untreated mice, whereas in the GH-treated group, an age-related decline was only seen in the old donors. Control testicular extracts had little effect on th ymulin release whereas GH treatment induced a definite thymulin-releas e inhibiting activity in the testicular homogenates of our animals whi ch increased progressively with the age of the testis donors. We concl ude that the MBH, AP and testis of the young mouse contain factors abl e to affect directly the endocrine activity of the thymic epithelium. The amount of these substances declines with age and seems to be modul ated by GH.