Arafah B M, Finegan H M, Roe J, Manni A, Pearson O H
Endocrinology. 1982 Aug;111(2):584-8. doi: 10.1210/endo-111-2-584.
The majority (87%) of N-nitrosomethylurea-induced rat mammary tumors regressed within 1 week after hypophysectomy (hypox). After a hypox-induced tumor regression, ovine PRL (oPRL), and 17 beta-estradiol (E2) were administered separately or in combination in order to define the individual role of these hormones in regulating tumor growth and influencing estrogen (E), progesterone (Pg), and PRL receptor (R) levels. Administration of E2 (2.5 micrograms twice daily) or oPRL (20 IU daily, started 5 days after hypox and continued for 10 days, resulted in stabilization of tumor growth. Simultaneous administration of E2 and oPRL resulted in a synergistic effect and reactivation of tumor growth. ER levels in mammary tumors were significantly lower than those in the control 15 days after hypox (P less than 0.01). Treatment with E2, oPRL, or both simultaneously had no significant effect on ER levels. A significant decline in PgR levels was noted at both 5 and 15 days after hypox. Whereas treatment with oPRL had no significant effect on PgR levels, E2 administration either alone or in combination with oPRL restored PgR levels to control values. PRLR levels were unchanged from control values at 5 days, but significantly declined (P less than 0.005) 15 days after hypox. Treatment with E2, oPRL, or both hormones simultaneously partially maintained PRLR and prevented the decline to the extremely low level noted in the untreated group. We conclude that the growth of nitrosomethylurea-induced rat mammary tumors is dependent on both E2 and PRL. There was a synergistic effect between E2 and PRL on tumor growth but not on ER, PgR, or PRLR. Neither E2 nor PRL had any significant effect on ER after hypox. PgR is under E2 control. Either E2 or PRL or both hormones were able to maintain PRLR in mammary tumors after hypox.
大多数（87%）N-亚硝基甲基脲诱导的大鼠乳腺肿瘤在垂体切除术后1周内消退。垂体切除诱导肿瘤消退后，分别或联合给予羊催乳素（oPRL）和17β-雌二醇（E2），以确定这些激素在调节肿瘤生长以及影响雌激素（E）、孕酮（Pg）和催乳素受体（R）水平方面的各自作用。给予E2（每日两次，每次2.5微克）或oPRL（每日20国际单位，垂体切除术后5天开始，持续10天）可使肿瘤生长稳定。同时给予E2和oPRL产生协同作用并使肿瘤生长重新激活。垂体切除术后15天，乳腺肿瘤中的雌激素受体（ER）水平显著低于对照组（P<0.01）。用E2、oPRL或两者同时治疗对ER水平无显著影响。垂体切除术后5天和15天，孕酮受体（PgR）水平均显著下降。而用oPRL治疗对PgR水平无显著影响，单独给予E2或E2与oPRL联合使用可使PgR水平恢复至对照值。催乳素受体（PRLR）水平在术后5天与对照值无变化，但在垂体切除术后15天显著下降（P<0.005）。用E2、oPRL或两种激素同时治疗可部分维持PRLR水平，并防止其降至未治疗组中所观察到的极低水平。我们得出结论，N-亚硝基甲基脲诱导的大鼠乳腺肿瘤生长依赖于E2和PRL。E2和PRL在肿瘤生长方面存在协同作用，但对ER、PgR或PRLR无协同作用。垂体切除术后，E2和PRL对ER均无显著影响。PgR受E2调控。垂体切除术后，E2、PRL或两种激素均可维持乳腺肿瘤中的PRLR水平。
