Nuclear Synthesis of Egg White Protein Messenger Ribonucleic Acids in Chick Oviduct: Effects of the Anti-estrogen Tamoxifen on Estrogen-, Progesterone-, and Dexamethasone-induced Synthesis

Tamoxifen is a potent anti-estrogen in the chicken oviduct [Sutherland, R., Mester, J., & Baulieu, E.E. (1977) Nature (London) 267, 434-435]. Its action on egg white protein gene transcription was studied in isolated nuclei under various hormonal conditions. Injected alone to estrogen-primed and then withdrawn chickens, tamoxifen was unable to trigger gene transcription. After its administration together with or 6 h after diethylstilbestrol (a synthetic estrogen), tamoxifen stopped or suppressed the estrogen-dependent increase of ovalbumin and conalbumin gene transcription. On the contrary, when tamoxifen was given with progesterone or with dexamethasone (a synthetic glucocorticosteroid), two steroids that also increased specific transcription of the ovalbumin and conalbumin genes, there was an amplification effect that lasted up to 24-30 h. These results demonstrate that tamoxifen is active at the transcriptional level when inhibiting estrogen action and when increasing progesterone and dexamethasone effects on protein synthesis [Catelli, M. G., Binart, N., Elkik, F., & Baulieu, E. E. (1980) Eur. J. Biochem. 107, 165-172; Le Bouc, Y. (1983) Thèse de 3ème cycle, Université Paris VII]. The complexity of hormone-anti-estrogen interactions on transcriptional efficiency was also illustrated by the greater amplifying effect of tamoxifen on conalbumin than on ovalbumin gene transcription and by the lack of potentiation by the anti-estrogen of dexamethasone-dependent ovomucoid gene transcription. The role of tamoxifen-estrogen receptor complexes in these responses is discussed in view of their differential amount in chromatin in the presence of estrogen or of progesterone.