Désarnaud F, Do Thi A N, Brown A M, Lemke G, Suter U, Baulieu E E, Schumacher M
INSERM U488, Le Kremlin-Bicêtre, France.
J Neurochem. 1998 Oct;71(4):1765-8. doi: 10.1046/j.1471-4159.1998.71041765.x.
To understand better the mechanisms by which progesterone (PROG) promotes myelination in the PNS, cultured rat Schwann cells were transiently transfected with reporter constructs in which luciferase expression was controlled by the promoter region of either the peripheral myelin protein-22 (PMP22) or the protein zero (P0) genes. PROG stimulated the P0 promoter and promoter 1, but not promoter 2, of PMP22. The effect of PROG was specific, as estradiol and testosterone only weakly activated promoters. Dose-response curves for stimulation of both promoter constructs by PROG were biphasic. RU486, a PROG antagonist, did not abolish the effect of PROG, but stimulated promoter activities by itself. In the human carcinoma cell line T47D expressing high levels of PROG receptor, PROG did not stimulate the P0 and PMP22 promoters, whereas the promoter region of the mouse mammary tumor virus was fully activated. Thus, the activation by PROG of promoter activity of two peripheral myelin protein genes is Schwann-cell specific.
为了更好地理解孕酮（PROG）促进周围神经系统髓鞘形成的机制，将培养的大鼠雪旺细胞用报告基因构建体进行瞬时转染，其中荧光素酶的表达由外周髓鞘蛋白22（PMP22）或零蛋白（P0）基因的启动子区域控制。PROG刺激P0启动子以及PMP22的启动子1，但不刺激启动子2。PROG的作用具有特异性，因为雌二醇和睾酮仅微弱激活启动子。PROG对两种启动子构建体的刺激剂量反应曲线呈双相性。PROG拮抗剂RU486并未消除PROG的作用，但其本身却刺激启动子活性。在高表达PROG受体的人癌细胞系T47D中，PROG并未刺激P0和PMP22启动子，而小鼠乳腺肿瘤病毒的启动子区域则被完全激活。因此，PROG对两种外周髓鞘蛋白基因启动子活性的激活具有雪旺细胞特异性。
