Ojeda S R, Hill J, Hill D F, Costa M E, Tapia V, Cornea A, Ma Y J
Division of Neuroscience, Oregon Regional Primate Research Center/Oregon Health Sciences University, Beaverton 97006, USA.
Endocrinology. 1999 Aug;140(8):3774-89. doi: 10.1210/endo.140.8.6941.
POU homeodomain genes are transcriptional regulators that control development of the mammalian forebrain. Although they are mostly active during embryonic life, some of them remain expressed in the postnatal hypothalamus, suggesting their involvement in regulating differentiated functions of the neuroendocrine brain. We show here that Oct-2, a POU domain gene originally described in cells of the immune system, is one of the controlling components of the cell-cell signaling process underlying the hypothalamic regulation of female puberty. Lesions of the anterior hypothalamus cause sexual precocity and recapitulate some of the events leading to the normal initiation of puberty. Prominent among these events is an increased astrocytic expression of the gene encoding transforming growth factor-alpha (TGF alpha), a tropic polypeptide involved in the stimulatory control of LHRH secretion. The present study shows that such lesions result in the rapid and selective increase in Oct-2 transcripts in TGF alpha-containing astrocytes surrounding the lesion site. In both lesion-induced and normal puberty, there is a preferential increase in hypothalamic expression of the Oct-2a and Oct-2c alternatively spliced messenger RNA forms of the Oct-2 gene, with an increase in 2a messenger RNA levels preceding that in 2c and antedating the peripubertal activation of gonadal steroid secretion. Both Oct-2a and 2c trans-activate the TGF alpha gene via recognition motifs contained in the TGF alpha gene promoter. Inhibition of Oct-2 synthesis reduces TGF alpha expression in astroglial cells and delays the initiation of puberty. These results suggest that the Oct-2 gene is one of the upstream components of the glia to neuron signaling process that controls the onset of female puberty in mammals.
POU 同源结构域基因是控制哺乳动物前脑发育的转录调节因子。尽管它们大多在胚胎期活跃，但其中一些在出生后的下丘脑仍有表达，这表明它们参与调节神经内分泌脑的分化功能。我们在此表明，Oct-2 是一种最初在免疫系统细胞中描述的 POU 结构域基因，是下丘脑对雌性青春期调节的细胞间信号传导过程的控制成分之一。下丘脑前部损伤会导致性早熟，并重现一些导致青春期正常启动的事件。这些事件中突出的是编码转化生长因子-α（TGFα）的基因的星形细胞表达增加，TGFα 是一种参与促性腺激素释放激素（LHRH）分泌刺激控制的促生长多肽。本研究表明，此类损伤会导致损伤部位周围含 TGFα 的星形细胞中 Oct-2 转录本迅速且选择性增加。在损伤诱导的青春期和正常青春期中，Oct-2 基因的 Oct-2a 和 Oct-2c 选择性剪接信使核糖核酸（mRNA）形式在下丘脑中的表达优先增加，2a mRNA 水平的增加先于 2c，且早于性腺类固醇分泌的青春期前激活。Oct-2a 和 2c 均通过 TGFα 基因启动子中包含的识别基序反式激活 TGFα 基因。抑制 Oct-2 的合成会降低星形胶质细胞中 TGFα 的表达，并延迟青春期的启动。这些结果表明，Oct-2 基因是控制哺乳动物雌性青春期开始的神经胶质细胞向神经元信号传导过程的上游成分之一。
