Contribution of Functional Groups of 19-Nor-Progestogens to Binding to Progesterone and Estradiol-17β Receptors in Rabbit Uterus

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Abstract
The structural elements of 19-nor-progestogens which may be essential for binding to progesterone and estradiol-17β(E2) receptors were) investigated in the rabbit uterine cytosol. The kinetic study showed that 19-nor-progestogens are competitive inhibitors of progesterone-receptor (8S) binding and E2-receptor binding. The affinities of steroids for the progesterone receptor were as follows: norethindrone (Ki of 2.3 × 10¬9M) > 5α-dihydronorethindrone > norethin-drone acetate > lynestrenol> 17α-ethynyl-estra-4-ene-3β, 17β-diol > ethynodiol diacetate (Ki of 1.3 × 10¬7M). The affinities of steroids for the E2 receptor were as follows: ethynodiol diacetate (Ki of 1.3 × 10¬7M)> 17α-ethynyl-estra-4-ene-3β, 17β-diol > norethin-drone acetate > norethindrone > 5α-dihydronore-thindrone > lynestrenol (Ki of 8.4 × 10¬7M). The results indicate that 3-ketone and 17β-hydroxyl groups, and the plane of ring A/B of 19-nor-progestogen are important for binding to the pro-gesterone receptor. The affinities of 19-nor-progesto-gens for the E2 receptor were very weak. Their affinities for the E2 receptor increased with addition of acetate or hydroxyl groups at the 3β and 17β positions, and were decreased by the elimination of a 3 oxygen function or the reduction of ring A. (Endocrinology100: 1566, 1977)

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