Breast Center, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Cancer Prev Res (Phila). 2010 Mar;3(3):312-21. doi: 10.1158/1940-6207.CAPR-09-0074. Epub 2010 Feb 9.
Early full-term pregnancy is an effective natural protection against breast cancer in both humans and experimental rodents. The protective effect of an early pregnancy is, in part, linked to changes in circulating hormones that are involved in both normal breast development and breast cancer. For example, a reduction in circulating growth hormone (GH) has been shown to protect rats from carcinogen-induced mammary tumors. We examined the ability of a full-term pregnancy to alter the endocrine GH/insulin-like growth factor-I (IGF-I) axis and how this change affected normal mammary gland function in two commonly used rat models (Sprague-Dawley and Wistar Furth). Circulating GH and IGF-I were measured in blood drawn every 30 minutes from parous and age-matched virgin female rats. Mean serum GH levels were significantly decreased (P < 0.01) in parous compared with age-matched virgin rats for both strains. Changes in GH levels were independent of estrous cycle, indicated by a significant (P < 0.05) reduction in circulating levels of GH during estrus and diestrus in both parous strains. Despite the decrease in circulating GH, pituitary GH mRNA levels were unaltered in parous rats. Circulating IGF-I and hepatic IGF-I mRNA were also unaltered by parity in either rat strain. Immunoblot analysis of mammary glands showed decreases in phosphorylation of signal transducer and activator of transcription 5A and Janus-activated kinase 2, suggesting reduced action of GH in the mammary gland. Therefore, although the parity reduction in circulating GH does not affect circulating IGF-I levels, it is possible that reduced GH acts directly at the mammary gland and may play a role in pregnancy protection from breast cancer.
早期足月妊娠是人类和实验性啮齿动物预防乳腺癌的有效自然保护措施。早期妊娠的保护作用部分与参与正常乳腺发育和乳腺癌的循环激素变化有关。例如，已经表明循环生长激素（GH）的减少可以保护大鼠免受致癌剂诱导的乳腺肿瘤。我们研究了足月妊娠改变内分泌 GH/胰岛素样生长因子-I（IGF-I）轴的能力，以及这种变化如何影响两种常用大鼠模型（Sprague-Dawley 和 Wistar Furth）的正常乳腺功能。从分娩和年龄匹配的处女雌性大鼠中每隔 30 分钟抽取一次血液，测量循环中的 GH 和 IGF-I。与年龄匹配的处女大鼠相比，两种品系的分娩大鼠的血清 GH 水平均显著降低（P < 0.01）。GH 水平的变化与发情周期无关，发情和发情期的 GH 循环水平显著降低（P < 0.05）表明了这一点。尽管循环 GH 减少，但分娩大鼠的垂体 GH mRNA 水平没有改变。两种大鼠品系的 IGF-I 和肝 IGF-I mRNA 也不受产仔的影响。乳腺免疫印迹分析显示信号转导和转录激活因子 5A 和 Janus 激活激酶 2 的磷酸化减少，表明 GH 在乳腺中的作用降低。因此，尽管循环 GH 的产仔减少不会影响循环 IGF-I 水平，但减少的 GH 可能直接作用于乳腺，并可能在妊娠预防乳腺癌方面发挥作用。
