Background The prevalence of thyroid nodules in a healthy population is high: in the German Papillon study, nationwide ultrasound screening of more than 90 000 people using 7AE5 MHz scanners revealed the presence of thyroid nodules in 33% of the normal population. A study employing more sensitive 13 MHz scanners has not been conducted so far.

Glucocorticoids play an essential role in maintaining basal and stress-related homeostasis, and lack of glucocorticoid action is incompatible with life in primates. Most known effects of glucocorticoids are mediated by the intracellular GR. The magnitude of a cell's response to glucocorticoids depends both on the hormone level it is exposed to and on its glucocorticoid sensitivity, i.e. the efficiency of GR-mediated signal transduction. In this review, we have summarized the multiple endogenous and exogenous factors that have been shown to be involved in this signaling cascade and, thus, to alter glucocorticoid sensitivity.

Alternative splicing of the human glucocorticoid receptor (hGR) pre-mRNA generates two highly homologous isoforms, termed hGRa and hGR. hGRa is a ligand-activated transcription factor which, in the hormone-bound state, modulates the expression of glucocorticoid-responsive genes by binding to specific glucocorticoid response element (GRE) DNA sequences. In contrast, hGRfi does not bind glucocorticoids and is transcriptionally inactive. We demonstrate here that hGR8 is able to inhibit the effects of hormone-activated hGRa on a glucocorticoid-responsive reporter gene in a concentration-dependent manner.['H]-Dexamethasone binding studies indicate that hGR*3 does not alter the affinity of hGRa for its hormonal ligand. The presence of hGR.8 in nuclear extracts and its ability to bind to a radiolabeled GRE oligonucleotide suggest that its inhibitory effect may be due to competition for GRE target sites.Reverse transcription-PCR analysis shows expression of hGRfi mRNA in multiple human tissues. These results indicate that hGRI3 may be a physiologically and pathophysiologically relevant endogenous inhibitor of glucocorticoid action, which may participate in defining the sensitivity of target tissues to glucocorticoids. They also underline the importance of distinguishing between the two receptor isoforms in all future studies of hGR function and the need to revisit old data. (J. Clin. Invest. 1995Invest. . 95:2435Invest. -2441

Glucocorticoids play an essential role in maintaining basal and stress-related homeostasis, and lack of glucocorticoid action is incompatible with life in primates. Most known effects of glucocorticoids are mediated by the intracellular GR. The magnitude of a cell's response to glucocorticoids depends both on the hormone level it is exposed to and on its glucocorticoid sensitivity, i.e. the efficiency of GR-mediated signal transduction. In this review, we have summarized the multiple endogenous and exogenous factors that have been shown to be involved in this signaling cascade and, thus, to alter glucocorticoid sensitivity.