Dissociated effects of tamoxifen on growth and on progesterone receptor induction in quail oviduct.
The estrogen agonist and antagonist activities of tamoxifen on growth and progesterone receptor induction were studied in the immature quail oviduct. Tamoxifen alone, when administered for 3 days at doses ranging from 0.01-10 mg/kg, had no effect on oviducal weight, DNA, and protein content, but significantly increased progesterone receptor concentration. When combined with estradiol benzoate (0.1 mg/kg daily for 3 days), tamoxifen completely inhibited the trophic action of estradiol while it only reduced the progesterone receptor concentration in the oviduct by 50%. This latter effect reflected more a reduction in the progesterone-responsive cell population of the tissue rather than a true estrogen antagonist effect on this specific protein induction. These results and previous data from this laboratory support the conclusions that in this model system: (1) the mechanisms involved in the induction of estrogen-sensitive cell proliferation and progesterone receptor synthesis are independent, and (2) the estrogen-antagonist activity of tamoxifen on cell proliferation is mediated through an estrogen receptor-independent pathway. Thus, the immature quail oviduct model system is particularly relevant to more detailed studies on the molecular modes of action of synthetic antiestrogens.
Laugier
C
C
INSERM U.205, Laboratoire de Physiologie-Pharmacodynamie, INSA 406, Villeurbanne, France.
Fanidi
A
A
Dufrene
L
L
Fayard
J M
JM
Pageaux
J F
JF
D000818:Animals; D003370:Coturnix / Q000502:physiology; D004958:Estradiol / Q000008:administration & dosage; D005260:Female; D008954:Models, Biological; D010057:Oviducts / Q000187:drug effects* / Q000254:growth & development; D011980:Receptors, Progesterone / Q000032:analysis / Q000187:drug effects*; D013629:Tamoxifen / Q000494:pharmacology*
D011980:Receptors, Progesterone; D013629:Tamoxifen; D004958:Estradiol