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J. Segal and B. R. Troen

ABSTRACT

The effect of age on the responsiveness of rat thymocytes to 3,5,3′-tri-iodothyronine (T3) was studied. It has been demonstrated previously that the plasma membrane-mediated effect of T3 to increase sugar uptake by rat thymocytes is influenced by age and sex. In both sexes, T3 given in vitro stimulated sugar uptake in cells from animals of 15 days of age, had no effect at 21 days and was again effective at 26 days. In the male, thymocytes from animals of 40 days of age and older were refractory to T3. However, in the female, T3, although less effective than in cells from 26-day-old animals, remained stimulatory in cells from 40- and 60-day-old rats. T3 had no effect in cells from animals of 90 days of age and older. In in-vivo studies in which female rats of 26, 60 and 90 days of age were first injected with T3 and 1 h later with [3H]2-deoxyglucose, the responsiveness of thymocytes to T3 also declined progressively with advancing age; T3 was most effective in cells from 26-day-old animals, less stimulatory in 60-day-old and essentially without effect in cells from 90-day-old animals. From these observations we have concluded that in both male and female rats the responsiveness of thymocytes to T3 declines progressively with age, and that this decline occurs at an earlier age in cells obtained from males.

J. Endocr. (1986) 110, 511–515

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Joseph Segal, B. R. Troen, and S. H. Ingbar

Studies of the influence of age and sex on the concentrations of total thyroxine (T4) and 3,5,3′-tri-iodothyronine (T3) in serum and on the free T4 and free T3 indices, were conducted in Sprague–Dawley rats of the CD strain varying in age between 10 days and 12 months. Both sex- and age-related differences were found. In all age-groups studied, serum T4 concentrations were higher in the male than in the female, whereas serum T3 concentrations were higher in the female. In both sexes, concentrations of T4 and T3 in serum reached a peak early in life, between the first and second month of age, and declined thereafter. In addition, in both sexes the intensity of thyroid hormone binding, as judged from values of the in-vitro uptake of T3, did not change with age, suggesting that free T4 and T3 concentrations in the serum display the same sex differences and age-related changes as do the concentrations of total T4 and T3. It remains to be determined whether these sex-and age-related alterations in serum thyroid hormone concentration are expressed in differences in the activity of various thyroid hormone-dependent processes.

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BS Moonga, OA Adebanjo, HJ Wang, S Li, XB Wu, B Troen, A Inzerillo, E Abe, C Minkin, CL Huang, and M Zaidi

The effects of the related cytokines interleukin-6 (IL-6), leukemia inhibitory factor (LIF) and oncostatin-M on bone resorption and cytosolic Ca(2+) signaling were compared in isolated rat osteoclasts. In the traditional disaggregated osteoclast (pit) assay, IL-6 and LIF, but not oncostatin-M, conserved the bone resorption otherwise inhibited by high extracellular [Ca(2+)] (15 mM). It produced a paradoxical, concentration-dependent stimulation of resorption by elevated extracellular Ca(2+). In the micro-isolated single osteoclast resorption assay, IL-6, high [Ca(2+)] or IL-6 plus high [Ca(2+)] all increased pit formation. In contrast, the IL-6 receptor (IL-6R)-specific agonist antibody MT-18 inhibited bone resorption in a concentration-dependent manner (1:500 to 1:500 000). MT-18 triggered cytosolic Ca(2+) signals in fura 2-loaded osteoclasts within approximately 10 min of application. Each cytosolic Ca(2+) transient began with a peak deflection that persisted in Ca(2+)-free, EGTA-containing extracellular medium, consistent with a release of intracellularly stored Ca(2+). This was followed by a sustained elevation of cytosolic [Ca(2+)] that was abolished in Ca(2+)-free medium, as expected from an entry of extracellular Ca(2+), and by the Ca(2+) channel antagonist Ni(2+). The inclusion of either IL-6 or soluble human (sh) IL-6R specifically reversed both the above effects of MT-18, confirming that both effects were specific for the IL-6R. The findings suggest that IL-6R activation by IL-6 stimulates osteoclastic bone resorption either by reversing the inhibitory effect of high extracellular Ca(2+) in stromal-containing systems or itself stimulating bone resorption along with Ca(2+) by micro-isolated osteoclasts. In contrast, activation of the IL-6R by an agonist antibody produces an inhibition of bone resorption and an associated triggering of the cytosolic Ca(2+) signals previously associated with regulation of bone resorptive function in other situations.