Tao X J, Tilly K I, Maravei D V, Shifren J L, Krajewski S, Reed J C, Tilly J L, Isaacson K B
Vincent Center for Reproductive Biology, Massachusetts General Hospital/Harvard Medical School, Boston 02114, USA.
J Clin Endocrinol Metab. 1997 Aug;82(8):2738-46. doi: 10.1210/jcem.82.8.4146.
Glandular epithelial cells of the human endometrium initiate apoptosis in the secretory phase of the cycle. To better understand the regulation of apoptosis in this paradigm of endocrine-regulated cell turnover, we studied the expression of the cell death regulatory genes, bax, bcl-2, and bcl-x, in human proliferative and secretory endometria relative to the absence or presence of apoptosis. As assessed by immunohistochemistry, levels of BAX protein were modest in proliferative endometrium and increased dramatically in the secretory phase when apoptosis was most prevalent. Expression of BAX was predominantly localized to epithelial cells of the functionalis layer of the secretory endometrium. In contrast, BCL-2 immunoreactivity was maximal during the proliferative phase and decreased in the secretory phase. Moreover, BCL-2 was topographically concentrated in the basalis layer. Immunoreactive BCL-X protein was observed mostly in glandular epithelial cells of the human endometrium. Compared with proliferative endometrium, secretory endometrium showed stronger BCL-X staining, especially in the functionalis layer. By Western blotting we confirmed that both proliferative and secretory endometrium expressed the long or antiapoptosis form as well as the short or proapoptosis form of the BCL-X protein. Taken together, our results demonstrate a coordinated pattern of expression of bcl-2 gene family members in human endometrium during the menstrual cycle, with a shift toward greater levels of the proapoptosis protein, BAX, occurring in glandular epithelial cells during the secretory phase of the cycle. Therefore, we conclude that cyclic changes in endometrial growth and regression may be precisely regulated by shifts in the ratio or balance of BCL-2 and related proteins in glandular epithelial cells.
人类子宫内膜的腺上皮细胞在月经周期的分泌期开始凋亡。为了更好地理解在这种内分泌调节的细胞更新模式中凋亡的调控机制，我们研究了细胞死亡调控基因bax、bcl-2和bcl-x在人类增殖期和分泌期子宫内膜中的表达情况，并与凋亡的有无进行了对比。通过免疫组织化学评估，增殖期子宫内膜中BAX蛋白水平适中，而在凋亡最为普遍的分泌期显著增加。BAX的表达主要定位于分泌期子宫内膜功能层的上皮细胞。相比之下，BCL-2免疫反应性在增殖期最高，在分泌期降低。此外，BCL-2在解剖学上集中于基底层。免疫反应性BCL-X蛋白主要在人类子宫内膜的腺上皮细胞中观察到。与增殖期子宫内膜相比，分泌期子宫内膜显示出更强的BCL-X染色，尤其是在功能层。通过蛋白质印迹法我们证实，增殖期和分泌期子宫内膜均表达BCL-X蛋白的长型或抗凋亡形式以及短型或促凋亡形式。综上所述，我们的结果表明，在月经周期中，人类子宫内膜中bcl-2基因家族成员的表达呈现出一种协调的模式，在周期的分泌期，腺上皮细胞中促凋亡蛋白BAX的水平会向更高水平转变。因此，我们得出结论，子宫内膜生长和消退的周期性变化可能由腺上皮细胞中BCL-2及相关蛋白的比例或平衡变化精确调控。
