In the liver of rainbow trout, the estrogen receptor gene is positively regulated by estradiol, and it is known that both basal and estradiol-stimulated expression of the estrogen receptor in the liver are inhibited by dexamethasone—an effect that is likely to take place at the transcriptional level (unpublished results). Therefore, it is possible that glucocorticoids also repress estrogen receptor expression at both central and pituitary levels, which could eventually interfere with the expression of estradiol-regulated genes. Such transcriptional interferences between endogenous steroid receptors on the expression of estrogen-dependent genes have already been documented in MCF-7 cells in the case of either progesterone or glucocorticoid receptors, an effect probably due to the fact that endogenous steroid receptors compete for factors that mediate their enhancer function. As estrogen receptor is required for the expression of the (3 subunit of GTH-2 in salmonids, such interactions could result in decreased GTH-2 synthesis under stressful conditions. Cortisol-induced inhibition of estrogen receptor and vitellogenin expression in the liver could explain the reduced quality of gametes observed in stressed rainbow trout.
In conclusion, this study confirms the widespread expression of rtGR in the brain-pituitary complex of the rainbow trout and shows that neurons and pituitary cells involved in the control of the reproductive axis are likely to be targets for cortisol. It is well known that the effects of steroid hormone receptors are directly linked to the intracellular receptor concentration. Therefore, the fact that rtGR immunoreactivity in the various target cells studied in this work is quite robust tends to indicate that these receptors are likely to induce significant physiological effects in those cells. Although it was initially believed that DNA binding through GRE was a prerequisite for GR-mediated genomic actions, there is growing evidence that many of the GR effects are mediated by protein-protein interactions. This is notably the case for the transrepression of GR on AP-1 driven genes. Therefore, the present study opens new research avenues for future work aimed at investigating at the molecular level the role of glucocorticoids on the expression of genes involved in the regulation of reproductive functions.