Induction of Cytosolic Progestin Binding Sites by Catecholestrogens in Rat Pituitary Gland and Uterus: Different Potencies of 2‐ and 4‐Hydroxyestradiol

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Abstract
The ability of catecholestrogens to induce cytosolic progestin binding sites in the hypothalamus, pituitary gland, and uterus of ovariectomized-adrenalectomized rats was demonstrated by the increase in high-affinity [3H]promegestone binding sites (Kd 1.39, 0.50, and 0.54 nM, respectively) following a single s.c. injection (26.4 .mu.g/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 .mu.g/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-hdyroxyestradiol. 2-Hydroxyestradiol 2,3-dibenzoate was ineffective in the pituitary gland up to a dose of 132 .mu.g/animal, whereas 4-hydroxyestradiol dibenzoate was equipotent to estradiol benzoate, showing a maximal induction of progestin binding sites at single doses in the range of 13.2-26.4 .mu.g/animal (equivalent to 10-20 .mu.g 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 .mu.g/animal (equivalent to 1-5 .mu.g of estradiol benzoate), 4-hdyroxyestradiol dibenzoate induced maximal levels of progestin receptors, and even 2-hydroxyestradiol dibenzoate, when given at a high dose (132.4 .mu.g/animal, equivalent to 100 .mu.g of estradiol benzoate), produced a slight increase in progestin binding sites.