The expression of beta 2-adrenergic receptors is up-regulated by glucocorticoids. In contrast, beta 1-adrenergic receptors display glucocorticoid-induced down-regulation. In rat C6 glioma cells, which express both of these subtypes of beta-adrenergic receptors, the synthetic glucocorticoid dexamethasone stimulates no change in the total beta-adrenergic receptor content, but rather shifts the beta 1:beta 2 ratio from 80:20 to 50:50. Radioligand binding and immunoblotting demonstrate a sharp decline in beta 1-adrenergic receptor expression. Metabolic labelling of cells with [35S]-methionine in tandem with immunoprecipitation by beta 1-adrenergic-receptor-specific antibodies reveals a sharp decline in the synthesis of the receptor within 48 h for cells challenged with glucocorticoid. Steady-state levels of beta 1-adrenergic-receptor mRNA declined from 0.47 to 0.26 amol/microgram of total cellular RNA within 2 h of dexamethasone challenge, as measured by DNA-excess solution hybridization. The stability of receptor mRNA was not influenced by glucocorticoid; the half-lives of the beta 1- and beta 2-subtype mRNAs were 1.7 and 1.5 h respectively. Nuclear run-on assays revealed the basis for the down-regulation of receptor expression, i.e. a sharp decline in the relative rate of transcription for the beta 1-adrenergic-receptor gene in nuclei from dexamethasone-treated as compared with vehicle-treated cells. These data demonstrate transcriptional suppression as a molecular explanation for glucocorticoid-induced down-regulation of beta 1-adrenergic receptors.

To study whether senescence-induced changes in the gut-associated lymphoid tissue (GALT) are mainly quantitative, several parameters were examined in three age groups of BALB/c mice (1-2, 12-14, and 24-28 months old). A substantial senescence-associated decline in the number of lymphoid cells was found in the mesenteric lymph nodes (MLN) and spleen (SPN), and especially in the Peyer's patches (PP), but not in the lamina propria (LP). The distribution of lymphocyte subsets in these tissues was also altered with an absolute reduction of T cells--in particular, a L3T4+ helper/inducer T-cell marker-bearing subset. These changes were most remarkable in PP, followed by MLN. The in vitro proliferative reactivity and the production of each isotype-specific immunoglobulin (Ig) by PP, MLN, and SPN were profoundly affected when T-cell-dependent (Td) B-cell mitogens were used, but minimally affected when T-cell-independent (Ti) B-cell mitogens were used. The isotype-specific Ig content of small-intestinal perfusates was also influenced by aging, but only to a minor extent, as exemplified by a decrease in IgA levels in the fasting condition. Thus, despite the defects in the quantity and distribution of lymphocytes in aged PP and MLN, the finding of little change in the total amount of secreted IgA in aged intestine suggests that gut IgA-mediated luminal immune responses could remain nearly unaltered with senescence. The constancy of intraluminal IgA levels could be of physiological significance in host defense at the gut mucosal surface in aged mice.

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