ESTROGEN-RECEPTOR MESSENGER-RNA EXPRESSION IN RAT HYPOTHALAMUS AS A FUNCTION OF GENETIC SEX AND ESTROGEN DOSE
ESTROGEN-RECEPTOR MESSENGER-RNA EXPRESSION IN RAT HYPOTHALAMUS AS A FUNCTION OF GENETIC SEX AND ESTROGEN DOSE
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DOI：
10.1210/endo-129-6-3180
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发表时间：
1991-12-01
期刊：
影响因子：
4.8
通讯作者：
PFAFF, DW
中科院分区：
文献类型：
--
作者：
LAUBER, AH;MOBBS, CV;PFAFF, DW
以前，我们表明，雌激素受体（ER）信使RNA（mRNA）水平下降的细胞中的内侧基底下丘脑卵巢切除（OVX）的雌性大鼠急性雌二醇治疗后。在这里，我们研究是否ER mRNA的水平仍然在雌二醇的持续长期存在的抑制，并质疑是否有一个系统的雌二醇浓度和ER mRNA水平的下降之间的关系。OVX雌性大鼠植入含有不同浓度雌二醇的硅橡胶胶囊2周。组织切片与[H-3]单链DNA探针杂交，所述探针从大鼠ER互补DNA的对应于类固醇结合结构域的区域制备，并且通过对特定下丘脑核中的细胞计数颗粒来评估相对mRNA水平。雌二醇诱导ER mRNA水平呈剂量依赖性降低。在使用的最高激素浓度下，腹内侧核（VLVM）的腹外侧方面的信息水平下降了57%，弓状核下降了62%。因此，雌鼠下丘脑雌激素受体mRNA表达下调呈现剂量依赖性，雌鼠下丘脑雌激素受体mRNA表达水平与雄鼠下丘脑雌激素受体mRNA表达水平之间是否存在差异，雌激素是否能下调雄鼠下丘脑雌激素受体mRNA水平。CAS大鼠的性别急性暴露于苯甲酸雌二醇（EB）的不同时间。同样，在女性中，EB显着降低ER mRNA水平VLVM的55%（18小时）和弓状核的74%（18小时）。有趣的是，对照CAS雄性动物的基础ER mRNA水平显著低于OVX雌性动物（VLVM中比雌性动物低52%;弓形虫中低56%），表明组成性表达水平存在性别差异。此外，EB未能显著下调男性ER信息水平。性别或EB处理对内侧杏仁核ER mRNA水平无显著影响。因此，第二项研究显示了ER mRNA的激素调节的性别差异和脑区特异性。这些结果表明，基础水平和调节的ER mRNA的差异可能是一个基板的雌激素受体浓度的性别差异在大鼠下丘脑，并进一步提高了性别差异的可能性，在浓度的核蛋白有关的ER基因表达的控制。
Previously, we showed that estrogen receptor (ER) messenger RNA (mRNA) levels are decreased in cells of the mediobasal hypothalamus of ovariectomized (OVX) female rats following an acute estradiol treatment. Here, we examined whether the level of ER mRNA remains depressed in the continued long-term presence of estradiol, and questioned if there is a systematic relationship between the concentration of estradiol and the decrease in ER mRNA level. OVX female rats were implanted for 2 weeks with silastic capsules containing various concentrations of estradiol. Tissue sections were hybridized with a [H-3] single-stranded DNA probe prepared from the region of the rat ER complementary DNA corresponding to the steroid binding domain, and relative mRNA level was assessed by counting grains over cells in specific hypothalamic nuclei. Estradiol induced a dose-dependent decrease in ER mRNA levels. Message levels declined in the ventrolateral aspect of the ventromedial nucleus (VLVM) by 57% and in the arcuate nucleus by 62% at the highest hormone concentrations used. Thus, ER mRNA down-regulation in female rat hypothalamus exhibits orderly dose dependence at a time following hormone treatment which ensures the system is at steady state.A second study determined if there exist differences in basal levels of ER mRNA expression between castrated (CAS) females and males, and if estradiol can down-regulate ER mRNA levels in male hypothalamus. CAS rats of both sexes were exposed acutely to estradiol benzoate (EB) for different periods of time. Again, in females, EB significantly decreased ER mRNA levels in VLVM by 55% (18 h) and in the arcuate nucleus by 74% (18 h). Interestingly, control CAS males had significantly lower basal ER mRNA levels than OVX females (52% lower than female levels in VLVM; 56% in arcuate), suggesting a sex difference in constitutive expression levels. Moreover, EB failed to down-regulate significantly ER message levels in males. There was no significant effect of sex or EB treatment on ER mRNA levels in medial amygdala. Thus, the second study shows sex differences and brain-region specificity in hormonal regulation of ER mRNA. These findings show that differences in basal levels and regulation of ER mRNA could be a substrate for sex differences in ER concentrations in the hypothalamus of the rat, and further raise the possibility of sex differences in concentrations of nuclear proteins related to the control of ER gene expression.