| To gain more insights into the mechanism of endogenous IGF-1 and estrogen action on thymic involution, this study was designed to expatiate mRNA expression patterns of thymic IGF-1, IGF-IR and estrogen receptors (ERs) in 3-, 7-and 13-month-old rats. At the same tune, changes of peripheral blood T cell function with age were observed. Furthermore, effects of cysteamine and daidzein on thymic involution and mRNA expression of thymic IGF-1, IGF-IR and ERs were tested in ovariectomized rats.1. The characteristics of rat thymic involution and changes of peripheral blood T cell function with ageThe thymic weight and thymic index of 3-month-old rat were significantly higher than that of 7- and 13-month-old rats (P<0.01, n=15), but no significant difference was observed between 3- and 7-month-old rats. This age-related change was mirrored by the histological results. Thymus of 3-month-old rats showed well-developed lobules with clear borderlines between cortex and medulla, compared with 7- and 13-month-old counterparts in which severe atrophic morphological characteristics were shown with vague borderlines and increased connective tissues.The aging progress of peripheral blood lymphocyte didn't coincide with thymic involution. The natural lymphocyte proliferation was not significantly different among 3 age groups of rats, so was serum IL-2 concentration. The lymphocyte transformation induced by PHA in 7-month-old rats was markedly higher than that in 3-month-old rats (P<0.05, n=5). All above results suggested that T cell senesced after the thymic involution, and T lymphocyte transformation at 3 months of age was inhibited temporarily.2. The mechanisms of IGF-1 and estrogen action on thymic involution in ratsRelative RT-PCR was used to detect mRNA expression in the present study. ThymicIGF-1R mRNA expression dropped sharply from 3 months of age onward (P<0.01, n=6), but didn't differ significantly between 7 and 13 months of age, and this positively correlated with thymic index (R2=0.727, P<0.001). This result implied that thymic IGF-1R may be a major modulator during rat thymic involution. On the contrary, thymic IGF-1 mRNA expression increased with age, which was negatively correlated with thymic index (R2=0.201, P=0.087), and with thymic IGF-1R mRNA expression (R2=0.203, P=0.076), suggesting a negative feedback loop of thymic IGF-1 and IGF-1R.ER a , ER β 1 and ER P 2 mRNA were firstly found to be expressed simultaneously in rat thymus. The mRNA expression of thymic ER a was not significantly different among 3 age groups. The relative abundances of ER β 1 and ER β 2 mRNA were comparable in rat thymus, both declined with age. This coincided with the increase of serum estrogen concentration. Above results indicated that estrogen may control thymic involution by down-regulating thymic ER β expression. The thymic ER a expressed consistently during thymic involution.3.The effects of cysteamine and daidzein on ovariectomized rat thymus and peripheral blood T lymphocyteDiet supplementation of cysteamine increased thymic weight (P<0.05, n=15) and thymic IGF-1R mRNA expression (P<0.01, n=6), but decreased thymic IGF-1 mRNA expression in ovariectomized rats. It suggested that cysteamine reverse the atrophic process of thymus by up-regulating thymic IGF-1R expression. Cysteamine enhanced natural proliferation of peripheral blood lymphocytes, but not PHA-stimulated lymphocyte transformation.Diet supplementation of cysteamine plus daidzein decreased (P=0.067, n=6) IGF-IR mRNA expression of ovariectomized rats compared to cysteamine treated group, although no differences in thymic weight and thymic index were observed between two groups. It implied that daidzein influence, to some extant, the effect of cysteamine on thymic gene expression.To summarize, during rat thymic involution in aging, endogenous IGF-1 and estrogen may control this progress mainly via their receptor mechanism, i.e. down-regulating IGF-IR and ER β gene expression respectively. Thymic IGF-1 and IGF-IR may form a...
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