Schmidt W N, Katzenellenbogen B S
Mol Cell Endocrinol. 1979 Aug;15(2):91-108. doi: 10.1016/0303-7207(79)90010-8.
This study investigates growth and the induction of progesterone-receptor synthesis in the immature (day 20--23) rat uterus after injection of different doses of 5 alpha-dihydrotestosterone (DHT) and testosterone (T) in long- and short acting injection vehicles. Moderate doses of T (300 microgram/day in saline for 3 days) elicit uterine growth (ca. 250% of control) that is abolished by concomitant injections of antiandrogen (1 mg flutamide/day or 8 mg DIMP/day) but is unaffected by injections of antiestrogens (60 microgram CI-628 or U11,100A/day). Uterine growth evoked by 17 beta-estradiol (3 microgram/day for 3 days) is, however, only antagonized with the antiestrogens but not antiandrogens. Experiments employing whole uteri in vitro indicate that the specific nuclear uptake of 10(-8) M [3H]T is markedly inhibited by the antiandrogens DIMP, flutamide, and the hydroxylated flutamide metabolite (LACT) [LACT greater than DIMP greater than FLUT] while the antiestrogens CI-628 and U11,100A are ineffective. In contrast, the specific nuclear uptake of 10(-8) M [3H]-estradiol is inhibited by only the antiestrogens and not antiandrogens. When very high (5 or 10 mg) doses of DHT Are administered in an oil-containing injection vehicle, nuclear translocation and cytoplasmic depletion of the estrogen receptor does occur and a uterotrophic response is elicited which is resistant to antagonism by antiandrogen. Likewise, the DHT-stimulated increase in progesterone-receptor content is not decreased by concomitant antiandrogen. Similar 5 or 10 mg doses of DHT, administered in a water-soluble dimethylsulfoxide vehicle, show little estrogen-receptor movement and the DHT-induced uterine growth and induction of progesterone-receptor synthesis is almost completely eliminated with antiandrogen. Regardless of the degree of uterine growth stimulation, however, the androgens are poor stimulators of uterine progesterone-receptor synthesis compared with estradiol. These results indicate that androgens may interact with both the androgen- and estrogen-receptor systems in the uterus in inducing uterine growth and that the nature of the cellular mechanism, i.e., whether the androgen- and/or estrogen-receptor system is involved, is dependent critically upon the in vivo dose of androgen and the mode of hormone administration.
本研究调查了在长效和短效注射载体中注射不同剂量的5α-二氢睾酮（DHT）和睾酮（T）后，未成熟（第20 - 23天）大鼠子宫的生长情况以及孕酮受体合成的诱导情况。中等剂量的T（300微克/天，溶于生理盐水，连续注射3天）可引起子宫生长（约为对照组的250%），同时注射抗雄激素（1毫克氟他胺/天或8毫克DIMP/天）可消除这种生长，但注射抗雌激素（60微克CI - 628或U11,100A/天）则无影响。然而，17β-雌二醇（3微克/天，连续注射3天）引起的子宫生长仅被抗雌激素拮抗，而不被抗雄激素拮抗。体外使用完整子宫进行的实验表明，抗雄激素DIMP、氟他胺和羟基化氟他胺代谢物（LACT）[LACT＞DIMP＞FLUT]可显著抑制10⁻⁸M [³H]T的特异性核摄取，而抗雌激素CI - 628和U11,100A则无效。相反，10⁻⁸M [³H] - 雌二醇的特异性核摄取仅被抗雌激素抑制，而不被抗雄激素抑制。当在含油注射载体中给予非常高（5或10毫克）剂量的DHT时，雌激素受体确实会发生核转位和细胞质耗竭，并引发子宫营养反应，该反应对抗雄激素的拮抗具有抗性。同样，DHT刺激引起的孕酮受体含量增加不会因同时使用抗雄激素而降低。在水溶性二甲基亚砜载体中给予类似的5或10毫克剂量的DHT，雌激素受体几乎没有移动，并且DHT诱导的子宫生长和孕酮受体合成的诱导几乎完全被抗雄激素消除。然而，无论子宫生长刺激的程度如何，与雌二醇相比，雄激素对子宫孕酮受体合成的刺激作用较弱。这些结果表明，雄激素在诱导子宫生长过程中可能与子宫中的雄激素和雌激素受体系统相互作用，并且细胞机制的性质，即是否涉及雄激素和/或雌激素受体系统，关键取决于体内雄激素的剂量和激素给药方式。
