AROMATASE INHIBITORS REGENERATE THE THYMUS IN AGING MALE-RATS
AROMATASE INHIBITORS REGENERATE THE THYMUS IN AGING MALE-RATS
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DOI：
10.1016/0192-0561(92)90115-2
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发表时间：
1992-05-01
期刊：
影响因子：
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通讯作者：
FITZPATRICK, FTA
中科院分区：
文献类型：
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作者：
GREENSTEIN, BD;DEBRIDGES, EF;FITZPATRICK, FTA
衰老大鼠的胸腺可以通过手术或化学阉割来再生，并且再生受到睾酮的抑制，睾酮可能至少部分通过其转化为雌二醇来发挥这种作用。已经尝试使用芳香酶系统抑制剂来再生完整衰老大鼠的胸腺，希望这种策略能够导致在免疫缺陷综合征的治疗中使用这种化学干预。在乙醚麻醉下对年轻成年和老年（18个月大）雄性大鼠进行睾丸切除，7天后进行皮下注射。将睾酮植入有机硅弹性体 (SILASTIC) 管中。一些大鼠接受睾酮和五倍过量的芳香酶抑制剂 1,4,6-雄甾三烯-3,17-二酮 (ATD)。一组年轻的完整大鼠接受含有 25 毫克 ATD 的植入物，一组 18 个月大的完整大鼠接受 125 毫克 ATD 或 25 毫克另一种更强大的芳香酶抑制剂 4-羟基雄烯二酮 (4-OH)。植入后第28天，处死大鼠，取出胸腺、脾脏、前列腺和精囊进行称重和组织学检查。此外，还测量了胸腺中的雌激素受体。睾丸切除术后胸腺增大，老年大鼠的胸腺又大大恢复。在衰老大鼠中，两种芳香酶抑制剂都恢复了胸腺，使胸腺在组织学上显得正常。此外，ATD 还使幼年完整动物的胸腺增大。使附属性器官恢复到在完整大鼠中测量的重量的睾酮剂量可以防止睾丸切除术对胸腺的影响，而在老年大鼠中，胸腺和脾脏中的 ATD 可以阻断睾酮的影响。在睾酮治疗的睾丸切除大鼠的胸腺中，可用的胞质雌激素受体减少，并且这种效应被 ATD 阻断，ATD 本身显然能够诱导雌激素受体。在衰老大鼠的胸腺中无法检测到受体，但在睾丸切除或 ATD 治疗的老年大鼠的胸腺细胞质中可以测量到受体。因此，无需借助手术或化学阉割就可以恢复完整的衰老大鼠的胸腺，并且这种操作可能有助于增强因衰老或疾病而削弱的免疫系统。
The thymus can be regenerated in aging rats by surgical or chemical castration and regeneration is inhibited by testosterone, which may exert this effect, at least in part, through its conversion to estradiol. An attempt has been made to regenerate the thymus in intact aging rats using inhibitors of the aromatase system, in the hope that this maneuver could lead to the use of such chemical intervention in the treatment of immunodeficiency syndromes. Young adult and aging (18-month-old) male rats were orchidectomized under ether anesthesia and 7 days later given s.c. implants of testosterone in silicone elastomer (SILASTIC) tubing. Some rats received testosterone together with a five-fold excess of the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD). One group of young intact rats received implants containing 25 mg ATD and a group of 18-month-old intact rats received 125 mg ATD or 25 mg of another, more powerful aromatase inhibitor 4-hydroxyandrostenedione (4-OH). On the 28th day after implanting, rats were killed and the thymus, spleen, prostate gland and seminal vesicles removed for weighing and histology. In addition, estrogen receptors were measured in the thymus. The thymus was enlarged after orchidectomy and greatly restored in aging rats. In aging rats, both aromatase inhibitors restored the thymus, which appeared normal histologically. In addition, ATD enlarged the thymus in young intact animals. Doses of testosterone which restored the accessory sex organs to weights measured in intact rats prevented the effects of orchidectomy on the thymus, and in old rats the effects of testosterone were blocked by ATD in both thymus and spleen. Available cytosolic estrogen receptors were reduced in thymus of testosterone-treated orchidectomized rats, and this effect blocked by ATD, which itself was apparently able to induce estrogen receptors. Receptors could not be detected in thymus from aging rats, but were measureable in cytosols from thymus of orchidectomized or ATD-treated old rats. It is therefore possible to restore the thymus in intact aging rats without recourse to surgical or chemical castration, and such a maneuver may possibly be of use to enhance an immune system weakened by aging or disease.