Melcangi R C, Magnaghi V, Cavarretta I, Zucchi I, Bovolin P, D'Urso D, Martini L
Department of Endocrinology, University of Milan, Italy.
J Neurosci Res. 1999 May 15;56(4):349-57. doi: 10.1002/(SICI)1097-4547(19990515)56:4<349::AID-JNR3>3.0.CO;2-H.
The present study has analyzed the effect of progesterone and its derivatives (dihydroprogesterone and tetrahydroprogesterone) on the gene expression of the peripheral myelin protein 22 utilizing in vivo and in vitro models. The data obtained indicate that tetrahydroprogesterone is able to stimulate the gene expression of peripheral myelin protein 22 both in vivo (in adult but not in old animals) and in Schwann cell cultures. An effect of this steroid, which is known to interact with the GABA(A) receptor, would not be surprising, since in the present study we show the presence in Schwann cells and in the sciatic nerve of the messengers for several subunits (alpha2, alpha3, beta1, beta2, and beta3) of the GABA(A) receptor. An effect of tetrahydroprogesterone is also evident on the gene expression of another myelin protein, the peripheral myelin protein zero. However, in this case also dihydroprogesterone, which is able to bind the progesterone receptor, is involved, both in old and adult animals, in the stimulation of messengers levels of this myelin protein. In conclusion, the present data show that the gene expression of two important peripheral myelin proteins can be influenced by progesterone derivatives. The hypothesis has been put forward that part of their effects might occur not through the classical progesterone receptor, but rather via an interaction with the GABA(A) receptor.
本研究利用体内和体外模型，分析了孕酮及其衍生物（二氢孕酮和四氢孕酮）对周围髓磷脂蛋白22基因表达的影响。所获得的数据表明，四氢孕酮在体内（在成年动物而非老年动物中）和雪旺细胞培养物中均能刺激周围髓磷脂蛋白22的基因表达。这种已知与GABA(A)受体相互作用的类固醇产生这样的作用并不奇怪，因为在本研究中我们显示了雪旺细胞和坐骨神经中存在GABA(A)受体几个亚基（α2、α3、β1、β2和β3）的信使分子。四氢孕酮对另一种髓磷脂蛋白——周围髓磷脂蛋白零的基因表达也有明显作用。然而，在这种情况下，能够结合孕酮受体的二氢孕酮在老年和成年动物中也参与了这种髓磷脂蛋白信使分子水平的刺激。总之，目前的数据表明，两种重要的周围髓磷脂蛋白的基因表达可受孕酮衍生物影响。有人提出假说，它们的部分作用可能不是通过经典的孕酮受体发生，而是通过与GABA(A)受体相互作用。
