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Induction of Cytosolic Progestin Binding Sites by Catecholestrogens in Rat Pituitary Gland and Uterus: Different Potencies of 2‐ and 4‐Hydroxyestradiol
Author(s) -
Kirchhoff Josef,
Reinhardt Walter,
Grünke Wolfgang,
Ghraf Rüdiger,
Ball Peter,
Knuppen Rudolf
Publication year - 1983
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1983.tb11307.x
Subject(s) - estradiol benzoate , medicine , endocrinology , progestin , uterus , pituitary gland , estrogen , estrogen receptor , cytosol , receptor , hypothalamus , chemistry , hormone , biology , biochemistry , ovariectomized rat , enzyme , cancer , breast cancer
The ability of Catecholestrogens to induce cytosolic progestin binding sites in the hypothalamus, pituitary gland and uterus of ovariectomised‐adrenal‐ectomised rats was demonstrated by the increase in high‐affinity [ 3 H]promegestone binding sites (K D 1.39,0.50 and 0.54 n M, respectively) following a single subcutaneous injection (26.4 μg/animal) of the 3, 4‐dibenzoate ester of 4‐hydroxyestradiol. The affinity and the time course of induction of these binding sites were very similar to those after a single injection of an equivalent dose (20 (μg/animal) of estradiol 3‐benzoate, exhibiting maximal receptor levels after 44 h. Widely differing efficacies in the induction of progestin binding sites were observed between the dibenzoate esters of 2‐ and 4‐hydroxyestradiol. 2‐Hydroxyestradiol 2, 3‐dibenzoate was ineffective in the pituitary gland up to a dose of 132 μg/ animal, whereas 4‐hydroxyestradiol dibenzoate was equi‐potent to estradiol benzoate, showing a maximal induction of progestin binding sites at single doses in the range of 13.2–26.4 μg/animal (equivalent to 10–20 μg of estradiol benzoate). As compared to the pituitary gland, the uterus was much more sensitive to the systemic administration of estrogen benzoates. At single doses in the range of 1.32–6.6 μg/animal (equivalent to 1–5 μg of estradiol benzoate), 4‐hydroxyestradiol dibenzoate induced maximal levels of progestin receptors and even 2‐hydroxyestradiol dibenzoate, when given at a high dose (132.4 μg/animal, equivalent to 100 μg of estradiol benzoate), produced a slight increase in progestin binding sites.