Estrogen-astrocyte-luteinizing hormone-releasing hormone signaling:: A role for transforming growth factor-β1
Estrogen-astrocyte-luteinizing hormone-releasing hormone signaling:: A role for transforming growth factor-β1
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DOI：
10.1095/biolreprod62.6.1710
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发表时间：
2000-06-01
影响因子：
3.6
通讯作者：
Brann, DW
中科院分区：
文献类型：
--
作者：
Buchanan, CD;Mahesh, VB;Brann, DW
本研究的目的是确定星形胶质细胞中能够调节LHRH神经分泌的因子。将分泌LHRH的细胞(GT1-7)暴露于C6胶质细胞和下丘脑星形胶质细胞(HA)的条件培养液(CM)中，可刺激LHRH的释放。C6和HA CM检测表明，转化生长因子-β(1)和3α-羟基-5α-孕烷-20-酮(3α，5α-THP)均存在于CM中，它们的水平与CM的LHRH释放活性平行增加。相反，在C6或HA CM中未检测到转化生长因子-α。通过超滤去除分子量为10 kDa的多肽，几乎消除了HA CM释放LHRH的能力。此外，特异性THF-β抗体的免疫中和作用可剂量依赖性地减弱CM的LHRH释放活性。大鼠下丘脑和GT1-7细胞表达转化生长因子-β受体和呋喃，一种将潜伏的转化生长因子-β(1)转化为活性转化生长因子-β-1的酶。逆转录-聚合酶链式反应和双重免疫荧光显示HAS中雌激素受体-α和ER-β的mRNA和蛋白表达，17-β-雌二醇(17-β-E-2)可增加HA-CM中活化和潜伏的转化生长因子-β(1)水平。ER拮抗剂ICI8280可完全阻断17β-E-2的作用。作为一个整体，这些研究提供了以前未描述的17β-E-2-转化生长因子-β(1)-LHRH信号通路的证据。
The purpose of this study was to identify factors from astrocytes that can regulate LHRH neurosecretion. Exposure of LHRH-secreting (GT1-7) cells to conditioned media (CM) from C6 glial cells and hypothalamic astrocytes (HA) stimulated LHRH release. Assays of C6 and HA CM revealed that transforming growth factor-beta(1) (TGF-beta(1)) and 3 alpha-hydroxy-5 alpha-pregnane-20-one (3 alpha,5 alpha-THP), both known LHRH secretagogues, were present in CM and their levels increased in parallel to the LHRH-releasing activity of CM. In contrast, TGF-alpha was undetectable in C6 or HA CM. Ultrafiltration to remove peptides with molecular weights >10 kDa virtually abolished the LHRH-releasing ability of the HA CM. Furthermore, immunoneutralization with a panspecific THF-beta antibody dose-dependently attenuated the LHRH-releasing activity of the CM. Rat hypothalamus and GT1-7 cells were demonstrated to express TGF-beta receptors as well as furin, an enzyme that converts latent TGF-beta(1) to active TGF-B-1. Estrogen receptor-alpha and ER-beta mRNA and protein were also demonstrated in HAs by reverse transcription-polymerase chain reaction and double immunofluorescence, and treatment with 17 beta-estradiol (17 beta-E-2) increased both active and latent TGF-beta(1) levels in HA CM. The effect of 17 beta-E-2 was completely blocked by the ER antagonist ICI8280. As a whole, these studies provide evidence of a previously undescribed 17 beta-E-2-TGF-beta(1)-LHRH signaling pathway.