Ishii Aiko, Nakamura Misa, Nakamura Atsushi, Takeda Koichi, Han Bo, Kakudo Kennichi
Department of Pathology, Wakayama Medical University, Wakayama, Japan.
Endocr J. 2006 Jun;53(3):317-24. doi: 10.1507/endocrj.k05-131. Epub 2006 May 19.
Calcitonin (CT) and calcitonin receptor (CTR) have been reported to play an important role in mammary tissue during pregnancy, lactation, and involution. In the present study, the expression and distribution of CTR mRNA in rat mammary tissue during pregnancy and lactation were investigated. As measured by real-time RT-PCR, CTR mRNA levels were increased only slightly during pregnancy, but increased markedly immediately postpartum and remained elevated through lactation, with the highest levels observed 14 days postpartum. In situ hybridization analysis showed that intense CTR mRNA signals were detected in the whole mammary gland. We performed immunohistochemistry to determine distribution of CTR in the mammary epithelium. CTR has been reported to act as an amylin receptor when heterodimerized with receptor activity modifying protein-1 (RAMP1) or RAMP3. mRNA expression of RAMP1 and RAMP3 in mammary tissue decreased during pregnancy and lactation, and amylin mRNA was undetectable, suggesting that up-regulated CTR in lactating mammary tissues binds CT rather than amylin. In primary cultures of mammary cells isolated from rat dams 14 days postpartum, CT produced a statistically significant decrease in thymidine incorporation. These results suggest that up-regulation of CTR during lactation may contribute to inhibition of mammary epithelial cell proliferation.
据报道，降钙素（CT）和降钙素受体（CTR）在妊娠、哺乳和乳腺 involution 期间的乳腺组织中发挥重要作用。在本研究中，研究了大鼠妊娠和哺乳期间乳腺组织中 CTR mRNA 的表达和分布。通过实时 RT-PCR 测量，CTR mRNA 水平在妊娠期间仅略有增加，但在产后立即显著增加，并在整个哺乳期保持升高，在产后 14 天观察到最高水平。原位杂交分析表明，在整个乳腺中检测到强烈的 CTR mRNA 信号。我们进行了免疫组织化学以确定 CTR 在乳腺上皮中的分布。据报道，当与受体活性修饰蛋白-1（RAMP1）或 RAMP3 异二聚化时，CTR 作为胰淀素受体起作用。乳腺组织中 RAMP1 和 RAMP3 的 mRNA 表达在妊娠和哺乳期间降低，并且未检测到胰淀素 mRNA，这表明哺乳期乳腺组织中上调的 CTR 结合 CT 而非胰淀素。在从产后 14 天的大鼠母鼠分离的乳腺细胞原代培养物中，CT 使胸苷掺入量产生统计学上的显著降低。这些结果表明，哺乳期 CTR 的上调可能有助于抑制乳腺上皮细胞增殖。
