Shyamala G
Division of Life Sciences, Lawrence Berkeley National Laboratory, University of California, Berkeley 94720, USA.
J Mammary Gland Biol Neoplasia. 1999 Jan;4(1):89-104. doi: 10.1023/a:1018760721173.
Progesterone was identified as a mammogenic hormone several years ago but until now its precise role in mammary development has remained obscure. Recently with the generation of several transgenic mouse models and development of reagents for analysis of progesterone receptor expression, the role of progesterone signaling in mammary development is becoming more clear. The most significant observations to emerge from these studies are (1) progesterone receptors (PR) are present in a heterogeneous manner in the epithelial cells and undetectable in the surrounding fat pad; (2) they are essential for lobuloalveolar and not for ductal morphogenesis; (3) progesterone signaling through progesterone receptors, leading to lobuloalveolar development, is initiated in the epithelium and may occur through paracrine mechanisms; and (4) a regulated expression of the two isoforms of progesterone receptor is critical for maintaining appropriate responsiveness to progesterone and hence, epithelial cell replicative homeostasis. These studies also reveal that the consequences of progesterone signaling through progesterone receptor may depend on the cell context, cell-cell and cell-extracellular matrix interactions, the dynamics of PR turnover and the fate of PR positive cells.
几年前，孕酮被确认为一种促乳腺生长激素，但直到现在，其在乳腺发育中的精确作用仍不清楚。最近，随着几种转基因小鼠模型的产生以及用于分析孕酮受体表达的试剂的开发，孕酮信号在乳腺发育中的作用变得更加清晰。这些研究中出现的最显著的观察结果是：（1）孕酮受体（PR）以异质性方式存在于上皮细胞中，而在周围脂肪垫中无法检测到；（2）它们对于小叶腺泡发育至关重要，而对于导管形态发生则不是必需的；（3）通过孕酮受体的孕酮信号传导导致小叶腺泡发育，起始于上皮细胞，可能通过旁分泌机制发生；（4）孕酮受体两种异构体的调控表达对于维持对孕酮的适当反应性以及上皮细胞复制稳态至关重要。这些研究还表明，通过孕酮受体的孕酮信号传导的后果可能取决于细胞环境、细胞间和细胞与细胞外基质的相互作用、PR周转的动力学以及PR阳性细胞的命运。
