Ethanol-induced alterations in the posttranslational processing, but not secretion of luteinizing hormone-releasing hormone in vitro.

Ethanol-induced alterations in the posttranslational processing, but not secretion of luteinizing hormone-releasing hormone in vitro.
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乙醇诱导翻译后加工的改变,但不影响体外黄体生成素释放激素的分泌。

DOI:
10.1111/j.1530-0277.1996.tb01092.x
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发表时间:
1996
期刊:
Alcoholism, clinical and experimental research
影响因子:
--
通讯作者:
Emanuele,N
Emanuele,N
中科院分区:
--
文献类型:
--
作者:
Uddin,S;Wilson,T;Emanuele,MA;Williams,D;Kelley,MR;Emanuele,N

文献摘要

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乙醇(EtOH)对雄性下丘脑-垂体生殖轴的影响是多方面的。尽管报告了直接性腺毒性,但也观察到下丘脑-垂体扰动。下丘脑取样的困难使得对EtOH诱导的促黄体生成素释放激素(LHRH)改变的直接研究充满了解释问题。为了规避这一点,我们进行了一系列实验,探索200 mg% EtOH在体外对GT 1 - 7细胞(一种新开发的分泌LHRH的神经细胞系)的影响。用含EtOH或不含EtOH的培养基处理细胞系2、6、24或48小时。在任何时间点,EtOH均未引起LHRH分泌的显著变化,尽管与对照相比,在EtOH暴露2小时后,分泌有增加的趋势。显著增加的总量(即,细胞加分泌的)pro-LHRH与仅暴露于EtOH 6小时后显著降低的细胞LHRH相结合,表明EtOH导致从生物无活性的pro-LHRH到生物活性的LHRH的加工的短暂降低。然而,即使在这个时间点,这些EtOH暴露细胞的LHRH分泌与对照细胞没有差异。在任何时间点,EtOH均未改变稳态LHRH mRNA水平。这些发现与先前使用下丘脑组织的体外数据一致,该数据同样证明EtOH对LHRH分泌无影响。结合体内证明EtOH可降低下丘脑-垂体门静脉血中LHRH水平,这些数据表明EtOH在下丘脑外部位和/或下丘脑内的非LHRH产生细胞上发挥作用。
The effects of ethanol (EtOH) on the male hypothalamic pituitary reproductive axis are multiple and varied. Although direct gonadal toxicity has been reported, hypothalamic‐pituitary perturbations have also been noted. The difficulty of sampling the hypothalamus has made direct investigation of EtOH‐induced alterations on luteinizing hormone‐releasing hormone (LHRH) fraught with interpretation problems. To circumvent this, we have conducted a series of experiments exploring the effect of 200 mg% EtOH in vitro on GT1‐7 cells, a newly developed LHRH secreting neural cell line. Cell lines were treated with EtOH‐containing or EtOH‐free media for 2,6,24, or 48 hr. EtOH caused no significant change in LHRH secretion at any time point, although there was a trend to increased secretion after 2 hr EtOH exposure when compared with control. Significantly increased total (i.e., cellular plus secreted) pro‐LHRH coupled with significantly reduced cellular LHRH after 6 hr only of EtOH exposure suggested that EtOH caused a transient decrease in processing from bioinactive pro‐LHRH to bioactive LHRH. However, even at this time point, LHRH secretion from these EtOH‐exposed cells was no different than from control cells. Steady‐state LHRH mRNA levels were not changed by EtOH at any time point. These findings are concordant with previous in vitro data using hypothalamic tissue that has similarly demonstrated no effect of EtOH on LHRH secretion. Taken together with the in vivo demonstration that EtOH reduces hypothalamic‐pituitary portal blood levels of LHRH, these data indicate that EtOH exerts its effect either at an extrahypothalamic locus and/or on non‐LHRH‐producing cells within the hypothalamus.