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ICI 182,780: a pure antiestrogen that affects behaviors and energy balance in rats without acting in the brain
Ist Teil von
American journal of physiology. Regulatory, integrative and comparative physiology, 1993-12, Vol.265 (6), p.1392-R1398
Ort / Verlag
United States
Erscheinungsjahr
1993
Quelle
MEDLINE
Beschreibungen/Notizen
G. N. Wade, J. D. Blaustein, J. M. Gray and J. M. Meredith
Department of Psychology, University of Massachusetts, Amherst 01003.
ICI 182,780 is one of a new class of steroidal antiestrogens that differs
from nonsteroidal antiestrogens, such as tamoxifen, in a number of
respects. 1) It is bound by estrogen receptors with a high affinity,
similar to that for estradiol. 2) It is a "pure" antiestrogen in that it
does not mimic any of the effects of estradiol. 3) This class of
antiestrogens does not seem to be bound by antiestrogen binding sites. 4)
ICI 182,780 may not be active in the brain after peripheral administration.
Indeed, ICI 182,780 blocked in vivo cell nuclear binding of [3H]estradiol
in uterus, pituitary, and adipose tissue but not in hypothalamus-preoptic
area. In vitro, ICI 182,780 competed for binding by neural estrogen
receptors with an affinity comparable with that for estradiol. When given
to ovariectomized rats, ICI 182,780 did not mimic any of the actions of
estradiol. Instead, ICI 182,780 treatment completely blocked the
uterotrophic effects of estradiol and attenuated the actions of estradiol
on linear growth, carcass fat content, fat pad weight, and sexual
receptivity. Treatment with ICI 182,780 also attenuated the estrogenic
effects of tamoxifen on food intake, body weight and composition, linear
growth, and uterine weight. These findings support the concept that, in
addition to its actions in the brain, estradiol can act peripherally to
modulate regulatory behaviors, energy balance, and estrous behavior. They
are also consistent with the hypothesis that nonsteroidal antiestrogens,
such as tamoxifen, affect energy balance via estrogen receptors, rather
than antiestrogen binding sites.