A paradoxical inhibitory effect of oestradiol-17beta on GnRH self-priming in pituitaries from tamoxifen-treated rats.
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.
Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain. fi1sacrj@uco.es
José E
JE
Sánchez-Criado
Carmina
C
Bellido
Rafaela
R
Aguilar
José C
JC
Garrido-Gracia
D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D000077267:Fulvestrant; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D009924:Organ Culture Techniques; D010052:Ovariectomy; D010636:Phenols; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology
D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010636:Phenols; D011720:Pyrazoles; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D000077267:Fulvestrant; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol