Lauber A H, Mobbs C V, Muramatsu M, Pfaff D W
Laboratory of Neurobiology and Behavior, Rockefeller University, New York, New York 10021.
Endocrinology. 1991 Dec;129(6):3180-6. doi: 10.1210/endo-129-6-3180.
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 [3H] 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.
此前，我们发现，急性雌二醇处理后，去卵巢（OVX）雌性大鼠中脑基底部下丘脑细胞中的雌激素受体（ER）信使核糖核酸（mRNA）水平会降低。在此，我们研究了在雌二醇持续长期存在的情况下，ER mRNA水平是否仍保持降低状态，并探讨了雌二醇浓度与ER mRNA水平降低之间是否存在系统关系。给OVX雌性大鼠植入含不同浓度雌二醇的硅橡胶胶囊，持续2周。用从大鼠ER互补DNA中对应类固醇结合域的区域制备的[3H]单链DNA探针与组织切片杂交，通过对特定下丘脑核中的细胞进行颗粒计数来评估相对mRNA水平。雌二醇诱导ER mRNA水平呈剂量依赖性降低。在所用的最高激素浓度下，腹内侧核腹外侧部分（VLVM）的信使水平下降了57%，弓状核下降了62%。因此，在激素处理后的某个时间点，雌性大鼠下丘脑的ER mRNA下调呈现出有序的剂量依赖性，这确保了系统处于稳态。第二项研究确定了去势（CAS）雌性和雄性之间ER mRNA表达的基础水平是否存在差异，以及雌二醇是否能下调雄性下丘脑的ER mRNA水平。对两性的CAS大鼠急性给予不同时间段的苯甲酸雌二醇（EB）。同样，在雌性大鼠中，EB显著降低了VLVM中ER mRNA水平的55%（18小时），以及弓状核中ER mRNA水平的74%（18小时）。有趣的是，对照CAS雄性大鼠的基础ER mRNA水平显著低于OVX雌性大鼠（VLVM中比雌性水平低52%；弓状核中低56%），表明在组成型表达水平上存在性别差异。此外，EB未能显著下调雄性大鼠的ER信使水平。性别或EB处理对内侧杏仁核中的ER mRNA水平没有显著影响。因此，第二项研究显示了在ER mRNA的激素调节方面存在性别差异和脑区特异性。这些发现表明，基础水平和ER mRNA调节的差异可能是大鼠下丘脑ER浓度性别差异的一个基础，并进一步增加了与ER基因表达控制相关的核蛋白浓度存在性别差异的可能性。
