Mondschein J S, Hammond J M, Weisz J
J Steroid Biochem. 1987 Jan;26(1):121-4. doi: 10.1016/0022-4731(87)90039-2.
The conversion of [3H]estradiol to 2-hydroxyestradiol (2-OH-E2) by homogenates of porcine ovarian follicles was assayed in vitro in the presence and absence of 10 and 100 microM concentrations of the following potential substrates or inhibitors of estrogen-2/4-hydroxylase (E-2/4-H): (1) estrogens; estrone (E1), estriol (E3) and 17 alpha-estradiol (17 alpha-E2), (2) catecholestrogens; 2-hydroxyestradiol (2-OH-E2), 4-hydroxyestradiol (4-OH-E2) and 2-hydroxyestrone (2-OH-E1); (3) 2-methoxyestradiol (2-MeO-E2); (4) halogenated estrogens; 2-bromoestradiol, (2-Bromo-E2) 4-bromoestradiol and 2,4-dibromoestradiol; (5) androgens; testosterone (T), dihydrotestosterone (DHT) and androstenedione; (6) progesterone; (7) epinephrine; (8) inhibitors of steroid aromatase; aminoglutethimide and 4-hydroxyandrostenedione and (9) SKF 525A, an inhibitor of cytochrome P-450. Progesterone and 2-Bromo-E2 were the two most effective inhibitors (2-OH-E2 formation = 4 and 5% of control at 100 microM and 29.6 and 17.4% at 10 microM of progesterone and 2-Bromo-E2, respectively). 2-MeO-E2 at 100 microM was nearly as effective as progesterone in inhibiting E-2/4-H activity but only caused about 50% inhibition at 10 microM. The three catecholestrogens reduced 2-OH-E2 formation to about the same degree (21-23% of control at 100 microM). The 2,4-dibromo-E2 was equipotent with the catecholestrogens while 4-bromo-E2 was about half as effective. The phenolic estrogens, potential substrates for the enzyme, reduced 2-OH-E2 formation to different degrees, with E3 being the most effective. Among the androgens, DHT was almost as effective an inhibitor as the catecholestrogens, T was about half as effective while androstenedione had no effect. Epinephrine and the two inhibitors of aromatase did not inhibit E-2/4-H activity. SKF 525A inhibited E-2/4-H activity but with a potency only about 1/10th that reported for liver.
在存在和不存在10和100微摩尔浓度的以下雌激素-2/4-羟化酶（E-2/4-H）的潜在底物或抑制剂的情况下，体外测定猪卵巢卵泡匀浆将[3H]雌二醇转化为2-羟雌二醇（2-OH-E2）的情况：（1）雌激素；雌酮（E1）、雌三醇（E3）和17α-雌二醇（17α-E2）；（2）儿茶酚雌激素；2-羟雌二醇（2-OH-E2）、4-羟雌二醇（4-OH-E2）和2-羟雌酮（2-OH-E1）；（3）2-甲氧基雌二醇（2-MeO-E2）；（4）卤代雌激素；2-溴雌二醇（2-Bromo-E2）、4-溴雌二醇和2,4-二溴雌二醇；（5）雄激素；睾酮（T）、二氢睾酮（DHT）和雄烯二酮；（6）孕酮；（7）肾上腺素；（8）类固醇芳香化酶抑制剂；氨鲁米特和4-羟基雄烯二酮；（9）细胞色素P-450抑制剂SKF 525A。孕酮和2-溴雌二醇是两种最有效的抑制剂（在100微摩尔时，2-OH-E2形成分别为对照的4%和5%；在10微摩尔时，孕酮和2-溴雌二醇分别为29.6%和17.4%）。100微摩尔的2-甲氧基雌二醇在抑制E-2/4-H活性方面几乎与孕酮一样有效，但在10微摩尔时仅引起约50%的抑制。三种儿茶酚雌激素将2-OH-E2形成降低到大致相同的程度（在100微摩尔时为对照的21%-23%）。2,4-二溴雌二醇与儿茶酚雌激素等效，而4-溴雌二醇的效果约为其一半。酚类雌激素作为该酶的潜在底物，不同程度地降低了2-OH-E2的形成，其中E3最有效。在雄激素中，二氢睾酮作为抑制剂几乎与儿茶酚雌激素一样有效，睾酮约为其一半，而雄烯二酮没有作用。肾上腺素和两种芳香化酶抑制剂不抑制E-2/4-H活性。SKF 525A抑制E-2/4-H活性，但其效力仅约为肝脏报道值的1/10。
