Gao L, Xu R K, Pang C S, Xu J P, Shan H M, Pang S F
Department of Physiology, Institute of Basic Medical Sciences, CAMS, PUMC, Beijing 100005, China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2001 Feb;23(1):49-53.
To examine the inhibitory effect of melatonin (MLT) on the development of pituitary prolactin-producing tumors (prolactinoma) induced by 17-beta-estradiol (E2), in vivo, and explore MLT's oncostatic mechanisms.
The prolactinomas were established by implanting E2-laden silastic capsules subcutaneously in Sprague-Dawley male rats. MLT doses 0.05, 0.25, 0.50, 1.00, and 2.00 mg/rat were administrated separately to 5 groups subcutaneously starting seven days prior to tumor induction for 97 days. The matched controls were given equal volumes of 4% alcohol in saline.
(1) The prolactinoma weights in 0.05, 0.25, 0.50, 1.00 and 2.00 mg MLT dose groups were 25.91% (P > 0.05), 48.78% (P < 0.01), 36.78% (P < 0.05), 31.04% (P > 0.05) and 35.22% (P > 0.05) respectively which were lower than that of control group; (2) The PRL mRNA levels of prolactinoma in 0.05, 0.25, and 0.50 mg MLT dose groups were 33.67% (P < 0.05), 25.51% (P < 0.05) and 41.84% (P < 0.01) respectively which were lower than that of control group as estimated by Northern Blot, and the in situ hybridization studies; (3) The DNA contents of prolactinoma in 0.05, 0.25 and 0.50 mg MLT dose groups were 40.73% (P < 0.001), 51.15% (P < 0.001) and 60.23% (P < 0.001) respectively which were lower than that of control group by laser scanning confocal microscopy; (4) Plasma peroxidative lipid contents in 0.05, 0.25, 0.50, 1.00 and 2.00 mg MLT dose groups were 26.45% (P < 0.05), 23.97% (P < 0.05), 47.11% (P < 0.001), 66.12%(P < 0.001) and 64.46% (P < 0.001) respectively which were lower than that of control group. The correlation coefficient between MLT doses and plasma peroxidative lipid contents was -0.8257 (P < 0.05).
MLT in suitable doses is able to inhibit the development of E2-induced prolactinoma by inhibiting the expression of PRL gene and the DNA synthesis. The link between MLT antioxidative action and its inhibitory effect on development of prolactinoma should be further investigated.
研究褪黑素（MLT）对17-β-雌二醇（E2）诱导的大鼠垂体催乳素瘤（泌乳素瘤）体内生长的抑制作用，并探讨其抑瘤机制。
将含E2的硅胶囊皮下植入Sprague-Dawley雄性大鼠体内建立泌乳素瘤模型。在诱导肿瘤前7天开始，分别给5组大鼠皮下注射剂量为0.05、0.25、0.50、1.00和2.00mg/大鼠的MLT，持续97天。匹配的对照组给予等体积的含4%酒精的生理盐水。
（1）0.05、0.25、0.50、1.00和2.00mg MLT剂量组的泌乳素瘤重量分别比对照组低25.91%（P>0.05）、48.78%（P<0.01）、36.78%（P<0.05）、31.04%（P>0.05）和35.22%（P>0.05）；（2）通过Northern印迹法和原位杂交研究估计，0.05、0.25和0.50mg MLT剂量组泌乳素瘤的PRL mRNA水平分别比对照组低33.67%（P<0.05）、25.51%（P<0.05）和41.84%（P<0.01）；（3）激光扫描共聚焦显微镜检测显示，0.05、0.25和0.50mg MLT剂量组泌乳素瘤的DNA含量分别比对照组低40.73%（P<0.001）、51.15%（P<0.001）和60.23%（P<0.001）；（4）0.05mg、0.25mg、0.50mg、1.00mg和2.00mg MLT剂量组的血浆过氧化脂质含量分别比对照组低26.45%（P<~0.05）、23.97%（P<0.05）、47.11%（P<0.001）、66.12%（P<0.001）和64.46%（P<0.001）。MLT剂量与血浆过氧化脂质含量之间的相关系数为-0.8257（P<0.05）。
适当剂量的MLT能够通过抑制PRL基因表达和DNA合成来抑制E2诱导的泌乳素瘤的生长。MLT的抗氧化作用与其对泌乳素瘤生长抑制作用之间的联系有待进一步研究。
