A Role for Progesterone in Breast Cancer *
A Role for Progesterone in Breast Cancer *
复制标题
黄体酮在乳腺癌中的作用*
DOI：
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发表时间：
1977
影响因子：
5.2
通讯作者：
K. Horwitz
中科院分区：
文献类型：
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作者：
W. McGuire;K. Horwitz
由于女性血液中雌激素和孕激素水平的周期性变化，以及这些激素在调节靶组织发育和生长方面的相互关系，因此不可避免地要研究孕激素对乳腺癌的影响。虽然孕酮本身不是一种致癌物，但它可能是一种有效的靶向特异性辅致癌物，可通过病毒或化学试剂诱导乳腺肿瘤。因此，该激素与肿瘤增强和肿瘤抑制有关。Huggins等人的开创性研究表明孕酮在刺激肿瘤生长中起作用。2 -4他们表明妊娠促进了二甲基苯并蒽（DMBA）诱导的大鼠乳腺肿瘤的生长。给完整的大鼠施用孕酮加速了肿瘤的出现，增加了肿瘤的数量，并增加了已建立肿瘤的生长速度。如果切除DMBA诱导的乳腺肿瘤大鼠的卵巢，同时在正中隆起处进行损伤以增加催乳素的释放，则肿瘤仅加速生长10-12天，然后消退，尽管催乳素水平保持稳定。~ .在这种情况下，负责维持肿瘤生长的卵巢因子尚未确定，但以下实验表明孕酮的重要性。妊娠刺激DMBA诱导的乳腺肿瘤的生长，而分娩和断奶之后是大量这些肿瘤的消退。妊娠期的肿瘤生长促进因子可能是胎盘泌乳素，而催乳素被认为是哺乳期肿瘤大小和生长的维持因素，因为如果阻止哺乳，肿瘤就会消退。然而，真实的情况更为复杂，因为卵巢切除术阻断了内源性或外源性催乳素对肿瘤生长的刺激作用，而注射孕酮则消除了这种阻断作用。一种解释是，在这种情况下催乳素对肿瘤的刺激依赖于孕酮，或者，在泌乳大鼠中发现的高水平的循环孕酮，在催乳素控制下，I2负责肿瘤生长。这并不一定意味着孕酮单独负责维持大鼠乳腺肿瘤的生长，因为在这些实验中，动物既有高催乳素水平，又有完整的肾上腺。另一方面，他们确实表明孕酮在刺激肿瘤生长中起着重要的生理作用。与上述孕酮的刺激作用相反，当与中等至大剂量的雌激素联合使用时，孕酮可诱导大鼠乳腺肿瘤消退或防止肿瘤出现。
Because of the cyclic changes of blood estrogen and progesterone levels that occur in females and the interrelationships among these hormones in regulating target tissue development and growth, it was inevitable that progesterone would be studied for its effect on breast cancer. Although progesterone itself is not a carcinogen, it may be a potent target-specific cocarcinogen for induction of mammary tumors by viral or chemical agents.l As such, the hormone has been implicated both in tumor enhancement and in tumor suppression. That progesterone plays a role in stimulating tumor growth is suggested by the pioneering studies of Huggins et al.2-4 They showed that pregnancy promoted the growth of dimethylbenzanthracene (DMBA)-induced rat mammary tumors. Administration of progesterone to intact rats accelerated the appearance of tumors, increased the numbers of tumors, and augmented the growth rate of established tumors. If DMBA-induced mammary tumor-bearing rats are ovariectornized and simultaneous lesions are placed in the median eminence to increase prolactin release, the tumor grows at an accelerated pace for only 10-12 days and then regresses, even though prolactin levels remain e l e ~ a t e d . ~ . ~ The ovarian factor responsible for maintaining tumor growth under these circumstances has not been identified, but the following experiments suggest the importance of progesterone. Pregnancy stimulates the growth of DMBA-induced mammary tumors, while parturition and weaning are followed by regression of a large number of these tum o r ~ . ~ , ~ , ~ The tumor growth-promoting factor of pregnancy is probably placental l a ~ t o g e n , ~ while prolactin has been implicated as being responsible for the maintenance of tumor size and growth during lactation, because tumors regress if suckling is prevented. I 0 * l I The true situation is more complex, however, because ovariectomy blocks the stimulatory effects of endogenous or exogenous prolactin on tumor growth, and injection of progesterone removes this block.I0 One interpretation would be that prolactin stimulation of tumors under these circumstances is dependent on progesterone or, alternatively, that the high levels of circulating progesterone found in the lactating rat, which are under prolactin control,I2 are responsible for the tumor growth. This does not necessarily mean that progesterone alone is responsible for maintaining rat mammary tumor growth, because in these experiments the animals had both high prolactin levels and intact adrenal glands. On the other hand, they do suggest that progesterone plays an important physiologic role in stimulating tumor growth. In contrast to the stimulatory effects of progesterone described above, progesterone can induce rat mammary tumor regression or prevent tumor appearance when combined with moderate to large doses of estrogen.2,13 In humans, the percentage of breast tumor regressions to a progesterone-estrogen combina-