Glucocorticoids Stimulate Ribonucleic Acid Degradation in Isolated Rat Thymic Lymphocytes in Vitro*

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Abstract
Glucocorticoids are known to stimulate lymphoid cell death, but little information is available regarding the biochemical mechanisms of adrenal steroid-induced lymphocytolysis. Previous work from our laboratory indicates that lymphocytes, which die in response to glucocorticoid, exhibit enhanced rates of cellular protein degradation. These findings encouraged us to study the turnover of other lymphocyte cellular macromolecules, namely RNA, as regulated by adrenal steroids. Thymic lymphocytes were pulse labeled in vitro in Eagle's Minimum Essential Medium supplemented with 10 μCi/ml [3H] uridine. Precursor incorporation into RNA was effectively stopped by a chase/dilution (1:20) of cells into fresh medium supplemented with 10 mM of both unlabeled uridine and cytidine. Cells were incubated in this medium for up to 4 h at 37 C with or without dexamethasone (Dex), and the remaining RNA-associated radioactivity was measured either by acid precipitation or with a multiple automated sample harvester. Control cells degraded RNA with a fractional degradative rate of 0.14 ± 0.01 h -1, whereas dexamethasone-treated cells had a fractional derivative rate of 0.21 ± 0.01 h-1. This represents a 50% stimulation of RNA degradation induced by Dex within 4 h of steroid treatment. Measurable stimulation of RNA degradation occurred 2.5 h after hormone administration in whole cells and 1.5 h when nuclear RNA turnover was quantitated. This glucocorticoid- induced RNA degradation was dependent on the concentration of hormone employed, with a half-maximal effective dose in the nanomolar range. Furthermore, this effect was glucocorticoid specific; only active glucocorticoids (Dex and cortisol) stimulated RNA degradation, whereas other steroids (17β-estradiol, progesterone, and 5α-dihydrotestosterone) did not have significant effects. Finally, glucocorticoid-induced degradation in thymocytes occurred before any measurable lymphocytolysis. We hypothesize that this glucocorticoid-induced RNA degradation is part of the degradation processes stimulated by the hormone that catalyzes the death of lymphoid cells.

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