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Biology of Reproduction 62, 1763-1771 (2000)
© 2000 Society for the Study of Reproduction, Inc.


Articles

Transcriptional Interference Between Glucocorticoid Receptor and Estradiol Receptor Mediates the Inhibitory Effect of Cortisol on Fish Vitellogenesis1

C. Lethimoniera, G. Flouriota, Y. Valotairea, O. Kaha, and B. Ducouret2,a

a Endocrinologie Moléculaire de la Reproduction, UPRES-A CNRS 6026, Endocrinologie Moléculaire des Poissons, INRA, Université de Rennes 1, 35042 Rennes cedex, France

In oviparous species, the synthesis of vitellogenin (Vg) takes place in the liver according to a strictly estrogen-dependent mechanism that first involves an up-regulation of the estrogen receptor (ER) by its own ligand. However, 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 decrease in plasma Vg levels. To investigate the mechanisms underlying these effects, in vivo and in vitro experiments were designed in rainbow trout (Oncorhynchus mykiss). The results demonstrate that cortisol implanted into maturing females caused a marked decrease of rainbow trout ER (rtER) and rainbow trout Vg (rtVg) mRNA levels in the liver. In vitro experiments on hepatocyte aggregates also showed that dexamethasone (Dex) caused a strong decrease in the basal and E2-stimulated rtER mRNA and to a lesser extent rtVg mRNA. 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 take place at the transcriptional level. This was further indicated by transfection experiments in CHO-K1 cells, which showed that rainbow trout glucocorticoid receptor (rtGR) strongly inhibited the E2-stimulated transcriptional activity of the rtER promoter. Taken together, these results indicate that the rtGR exerts a transcriptional interference on the expression of the rtER that may explain some of the negative effects of stress or cortisol on vitellogenesis.

First decision: 6 December 1999.

1 This work was supported by the Ministère de l'Education Nationale et de la Recherche, the CNRS, the INRA, and the Fondation Langlois.

2 Correspondence: B. Ducouret, Endocrinologie Moléculaire de la Reproduction, UPRES-A CNRS 6026, Campus de Beaulieu, Bat 13, 35042 Rennes cedex, France. FAX: 33 2 99 67 94; bernadette.ducouret{at}univ-rennes1.fr




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