Lin Y C, Loring J M, Villee C A
Cancer Res. 1982 Mar;42(3):1015-9.
Prolonged administration of estrogen to hamsters by implanted pellets induces not only renal adenocarcinomas but also enlarges pituitaries with hyperplastic and neoplastic changes, especially in the pars intermedia. The pituitaries of the diethylstilbestrol-implanted animals weigh 90 to 150 mg; those of control animals without diethylstilbestrol pellets weigh 7 to 12 mg. The enlarged pituitaries have 9.7 x 10(-10) M progesterone receptors compared to 0.75 x 10(-10) M in the controls. Castrated male hamsters were hypophysectomized, implanted with diethylstilbestrol pellets, fed laboratory chow ad libitum, and given 5% glucose in water to drink. New pellets were implanted every 3 months, and the animals survived for 12 to 15 months. At autopsy, none of the animals had a tumor. Sixty-two of 65 control castrated males with the same schedule of pellet implantation developed tumors. Hypophysectomized castrated males implanted with diethylstilbestrol pellets were given daily injections of 1 microgram each of follicle-stimulating hormone, luteinizing hormone, and prolactin; or with 0.9% NaCl solution. These animals survived for 12 to 15 months, but none developed kidney tumors. Other castrated males were hypophysectomized and implanted with diethylstilbestrol pellets, and 2 months later tumor tissues were transplanted under the kidney capsule. Eighty days later, no tumors were evident in the kidneys of these animals. Control castrated males were implanted with diethylstilbestrol pellets, and 2 months later tumor tissue was transplanted under the kidney capsule. Between 60 and 85 days later, 13 of the 15 controls had developed renal tumors. The concentrations of follicle-stimulating hormone, luteinizing hormone, and prolactin were measured by radioimmunoassays. The concentrations of circulating follicle-stimulating hormone and luteinizing hormone in animals with diethylstilbestrol implants decreased with time and, by 7 months, were similar to those in hypophysectomized animals. The concentration of prolactin in animals with diethylstilbestrol pellets increased with time and reached twice the value in the control animals without diethylstilbestrol pellets. These studies suggest that some factor secreted by the pituitary may be involved as a promoter or a cocarcinogen in the estrogen induction of kidney tumors.
通过植入药丸给仓鼠长期施用雌激素，不仅会诱发肾腺癌，还会使垂体增大并出现增生性和肿瘤性变化，尤其是在垂体中间部。植入己烯雌酚的动物的垂体重量为90至150毫克；未植入己烯雌酚药丸的对照动物的垂体重量为7至12毫克。增大的垂体含有9.7×10⁻¹⁰M的孕酮受体，而对照动物的为0.75×10⁻¹⁰M。对去势雄性仓鼠进行垂体切除，植入己烯雌酚药丸，随意喂食实验室饲料，并给予5%葡萄糖水溶液饮用。每3个月植入新的药丸，动物存活12至15个月。尸检时，所有动物均未出现肿瘤。按照相同的药丸植入方案，65只对照去势雄性仓鼠中有62只发生了肿瘤。给植入己烯雌酚药丸的垂体切除去势雄性仓鼠每日注射1微克促卵泡激素、促黄体生成素和催乳素；或注射0.9%氯化钠溶液。这些动物存活12至15个月，但均未发生肾肿瘤。其他去势雄性仓鼠进行垂体切除并植入己烯雌酚药丸，2个月后将肿瘤组织移植到肾包膜下。80天后，这些动物的肾脏中未出现明显肿瘤。给对照去势雄性仓鼠植入己烯雌酚药丸，2个月后将肿瘤组织移植到肾包膜下。60至85天后，15只对照仓鼠中有13只发生了肾肿瘤。通过放射免疫分析法测定促卵泡激素、促黄体生成素和催乳素的浓度。植入己烯雌酚的动物体内循环促卵泡激素和促黄体生成素的浓度随时间下降，到7个月时，与垂体切除动物的浓度相似。植入己烯雌酚药丸的动物体内催乳素的浓度随时间增加，达到未植入己烯雌酚药丸的对照动物的两倍。这些研究表明，垂体分泌的某些因子可能作为启动子或共致癌物参与雌激素诱导肾肿瘤的过程。
