| One of the earliest detectable effects of the glucocorticoid hormones on mouse L cells is a decrease in the proportion of ribosomes which are engaged as polysomes (i.e., the polysome content). During the first 60 minutes of exposure of the cells to the steroid, their polysome content begins to decline, falling within 5 hours from a high steady state level (78%), characteristic of rapidly growing cells, to a low steady state level (62%), characteristic of quiescent cells. Associated with this hormone-related change is a partial suppression of the rate of protein synthesis. The decrease in polysome content, like the hormone-induced increase in L cell glutamine synthetase, is both glucocorticoid-specific and concentration dependent.;Concomitant with the early change in L cell polysome content is an approximate 4-fold decrease in the extent of phosphorylation of protein S6 of the 40S ribosomal subunit. This response is similarly independent of nuclear alterations in transcription induced by the steroid. In addition, the general distribution of ribosomes having decreased S6 phosphorylation among all size classes of polysomes indicates that reduced phosphorylation of this protein is not tantamount to ribosome inactivation. Rather it seems to be associated with the regulation of ribosomal activity (e.g., selective initiation) during growth-suppression by the hormone.;Experiments designed to examine the mechanism of the early polysome decrease indicate that the response is not due to a limitation in the amount of functional mRNA. Rather, the glucocorticoids appear to regulate protein synthesis by reducing the rate of translational initiation. This is supported by the findings that hormone-treated cells have a lower rate of polysome reformation in vivo as well as a larger proportion of nonactive monosomes (vacant couples) in their 80S ribosome fraction than untreated cells. Additional studies employing glucocorticoid antagonists or other modulators of glucocorticoid action (e.g., pyridoxal phosphate) demonstrate that the decrease in polysome content is mediated solely within the cytoplasm of the cell. Thus, unlike many cellular responses to steroid hormones, such as the induction of L cell glutamine synthetase by glucocorticoids, the change in polysomes does not depend upon transcriptional adjustments initiated by the hormone. |
