Kahn D, Svanas G W, Eagon P K, Makowka L, Podesta L, Chapchap P, Starzl T E, Van Thiel D H
Department of Medicine, University of Pittsburgh, PA 15261.
J Lab Clin Med. 1988 Aug;112(2):232-9.
Because biochemical "feminization" of the liver in males is observed with hepatic regeneration and because the hepatic regenerative response in females is greater than that in males, the possibility that antiandrogens might potentiate liver regeneration was investigated. Before 70% hepatectomy, adult male Wistar rats were treated with cimetidine, an antiandrogenic H2 antagonist, at doses up to 10 times greater than those used clinically. Control animals received either the saline vehicle or ranitidine, an H2 antagonist without antiandrogenic properties. Treatment with cimetidine reduced the hepatic cytosolic androgen receptor content compared with ranitidine treatment. Hepatectomy caused a further reduction in androgen receptor activity in all groups. Hepatic cytosolic estrogen receptor activity was comparable in all groups throughout the study. Moreover, the rate of liver growth and the levels of ornithine decarboxylase and thymidine kinase activity induced as part of the regenerative response were similar in all groups. Thus, cimetidine, despite its ability to bind to androgen receptors, and ranitidine, an H2 receptor antagonist without antiandrogen action, do not modulate the hepatic regenerative response to a 70% partial hepatectomy.
由于在肝脏再生过程中观察到雄性肝脏出现生化“女性化”，且雌性肝脏的再生反应大于雄性，因此研究了抗雄激素是否可能增强肝脏再生。在进行70%肝切除术前，成年雄性Wistar大鼠接受西咪替丁（一种抗雄激素的H2拮抗剂）治疗，剂量最高可达临床使用剂量的10倍。对照动物接受生理盐水载体或雷尼替丁（一种无抗雄激素特性的H2拮抗剂）。与雷尼替丁治疗相比，西咪替丁治疗降低了肝脏胞质雄激素受体含量。肝切除术导致所有组的雄激素受体活性进一步降低。在整个研究过程中，所有组的肝脏胞质雌激素受体活性相当。此外，所有组的肝脏生长速率以及作为再生反应一部分诱导产生的鸟氨酸脱羧酶和胸苷激酶活性水平相似。因此，尽管西咪替丁有能力与雄激素受体结合，而雷尼替丁是一种无抗雄激素作用的H2受体拮抗剂，但它们都不会调节肝脏对70%部分肝切除术的再生反应。
