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  • Title: A paradoxical inhibitory effect of oestradiol-17beta on GnRH self-priming in pituitaries from tamoxifen-treated rats.
    Author: Sánchez-Criado JE, Bellido C, Aguilar R, Garrido-Gracia JC.
    Journal: J Endocrinol; 2005 Jul; 186(1):43-9. PubMed ID: 16002534.
    Abstract:
    Two-week ovariectomized (OVX) rats were injected over three days with 25 microg oestradiol benzoate (EB), 3 mg tamoxifen (TX) and 0.2 ml oil and their pituitaries were harvested for incubation experiments. Pituitaries from EB- and TX-treated OVX rats exhibited GnRH self-priming when incubated with their corresponding ligand. However, incubation of pituitaries with different ligands yielded divergent results: when pituitaries from EB-treated rats were incubated with 10(-7) M TX they displayed GnRH self-priming, whereas incubation of pituitaries from TX-treated rats with 10(-8) M oestradiol-17beta (E2) blocked GnRH self-priming. Further studies to analyse the latter finding revealed that: (a) E2 inhibited TX-induced GnRH self-priming in a dose-dependent manner while 10(-8) M oestradiol-17alpha did not; (b) co-incubation of E2 with the pure anti-oestrogen ICI 182,780, but not with the selective oestrogen receptor modulator TX, reversed the E2 inhibitory effect; (c) the oestrogen receptor (ER)-alpha selective agonist propylpyrazole triol, but not the ERbeta selective agonist diarylpropionitrile, mimicked the inhibitory effect of E2; (d) the analogue membrane-impermeable conjugated E2-BSA also inhibited TX-induced GnRH self-priming; and (e) a 15-min exposure of the pituitaries to E2 was sufficient to inhibit the GnRH self-priming elicited by TX. Although other explanations may exist, altogether these results suggested that E2, via an ER different from classical ER, inhibits the GnRH self-priming elicited by TX.
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