TY - JOUR
T1 - Nonsteroidal antiestrogens
T2 - Their biological effects and potential mechanisms of action
AU - Jordan, V. Craig
AU - Dix, Clive J.
AU - Naylor, Karen E.
AU - Prestwich, Graham
AU - Rowsby, Linda
PY - 1978/1/1
Y1 - 1978/1/1
N2 - The uterotropic and ontiuterotropic effects of a variety of structural derivatives of the nonsteroidal antiestrogen tamoxifen have been determined in the rat and the mouse. One derivative, monohydroxytamoxifen, was found to be a potent antiestrogen in the rat, with a high affinity for the estrogen receptor. Various techniques of sucrose density gradient analysis were used to demonstrate that estradiol and tamoxifen bind to the rat uterine cytoplasmic estrogen receptor. Estrogens and antiestrogens provoke the translocation of estrogen receptors to the nucleus and deplete the cytoplasmic estrogen receptor pool for short or long periods depending on the dose administered. Estradiol stimulates endometrial hyperplasia with an increase in total uterine DNA content, whereas tamoxifen stimulates endometrial hypertrophy with only a slight increase in uterine DNA content. It is concluded that the molecular shape of the ligand that binds to the estrogen receptor determines antiestrogenlc activity.
AB - The uterotropic and ontiuterotropic effects of a variety of structural derivatives of the nonsteroidal antiestrogen tamoxifen have been determined in the rat and the mouse. One derivative, monohydroxytamoxifen, was found to be a potent antiestrogen in the rat, with a high affinity for the estrogen receptor. Various techniques of sucrose density gradient analysis were used to demonstrate that estradiol and tamoxifen bind to the rat uterine cytoplasmic estrogen receptor. Estrogens and antiestrogens provoke the translocation of estrogen receptors to the nucleus and deplete the cytoplasmic estrogen receptor pool for short or long periods depending on the dose administered. Estradiol stimulates endometrial hyperplasia with an increase in total uterine DNA content, whereas tamoxifen stimulates endometrial hypertrophy with only a slight increase in uterine DNA content. It is concluded that the molecular shape of the ligand that binds to the estrogen receptor determines antiestrogenlc activity.
UR - http://www.scopus.com/inward/record.url?scp=0018138311&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0018138311&partnerID=8YFLogxK
U2 - 10.1080/15287397809529666
DO - 10.1080/15287397809529666
M3 - Article
C2 - 207880
AN - SCOPUS:0018138311
SN - 0098-4108
VL - 4
SP - 363
EP - 390
JO - Journal of Toxicology and Environmental Health
JF - Journal of Toxicology and Environmental Health
IS - 2-3
ER -