Transcriptional interference between glucocorticoid receptor and estradiolreceptor mediates the inhibitory effect of cortisol on fish vitellogenesis

In oviparous species, the synthesis of vitellogenin (Vg) fakes place in the liver according to a strictly estrogen-dependent mechanism that first invo lves an up-regulation of the estrogen receptor (ER) by its own ligand. Howe ver, reports from the literature indicate that in trout stress or cortisol may cause a reduction of cytosolic E2-binding sites in the liver and a decr ease in plasma Vg levels. To investigate the mechanisms underlying these ef fects, in vivo and in vitro experiments were designed in rainbow trout (Onc orhynchus mykiss). The results demonstrate that cortisol implanted into mat uring females caused a marked decrease of rainbow trout ER (rtER) and rainb ow trout Vg (rtVg) mRNA levels in the liver. In vitro experiments on hepato cyte aggregates also showed that dexamethasone (Dex) caused a strong decrea se in the basal and E2-stimulated rtER mRNA and to a lesser extent rtVg mRN A. These effects were specific as no other hormones were able to mimic the inhibitory action of Dex. A study of rtER mRNA stability indicated that the effects of glucocorticoids are likely to fake place at the transcriptional level. This was further indicated by transfection experiments in CHO-K-1 c ells, which showed that rainbow trout glucocorticoid receptor (rtGR) strong ly inhibited the Ea-stimulated transcriptional activity of the rtER promote r. Taken together, these results indicate that the rtGR exerts a transcript ional interference on the expression of the rtER that may explain some of t he negative effects of stress or cortisol on vitellogenesis.