Thyroid hormones and estrogen affect oxytocin gene expression in hypothalamic neurons
Thyroid hormones and estrogen affect oxytocin gene expression in hypothalamic neurons
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DOI：
10.1046/j.1365-2826.1999.00250.x
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发表时间：
1999-01-01
影响因子：
3.2
通讯作者：
Pfaff, DW
中科院分区：
文献类型：
--
作者：
Dellovade, TL;Zhu, YS;Pfaff, DW
催产素（OT）基因启动子具有复合激素反应元件，使得核受体的类固醇/甲状腺激素超家族的几个成员可以在体外在该反应元件处相互作用。为了在脑组织中研究这一点，与前述行为实验平行，我们使用原位杂交组织化学来寻找下丘脑中雌激素和甲状腺激素对OT mRNA的相互作用。在卵巢切除（OVX）大鼠中，高剂量的三碘甲状腺原氨酸（T3）升高室旁核（PVN）中的OT mRNA水平，而单独用苯甲酸雌二醇（EB）处理没有显著影响，相反，除OVX外还切除甲状腺（TX）的动物在EB处理后PVN中的OT基因表达水平显著升高。也就是说，内源性甲状腺激素干扰EB-诱导基因表达。此外，在OVX和TX/OVX动物中，当T3与EB一起给予时，OT基因表达降低至与对照组相当的值。PVN的特定细分对T3和EB治疗的反应不同，表明该核中含有OT的神经元具有显着的异质性。因此，与甲状腺激素减少雌激素刺激行为的方式平行，也可能相关，内源性或外源性甲状腺激素干扰雌激素刺激OT mRNA。这些数据表明，核蛋白，转录因子之间的竞争，在下丘脑神经元。
The oxytocin (OT) gene promoter has a composite hormone response element, such that several members of the steroid/thyroid hormone superfamily of nuclear receptors can interact at this response element in vitro. To investigate this in brain tissue, parallel to foregoing behavioural experiments, we used in situ hybridization histochemistry to seek interactions between estrogen and thyroid hormones on OT mRNA in the hypothalamus. In ovariectomized (OVX) rats, high doses of triiodothyronine (T3) elevated OT mRNA levels in the paraventricular (PVN) nucleus, while treatment with estradiol benzoate (EB) alone had no significant effect, in contrast, animals that were thyroidectomized (TX) in addition to OVX had dramatically elevated levels of OT gene expression in the PVN following EB treatment. That is, endogenous thyroid hormones interfered with EB-induction of gene expression. Moreover, in both OVX and TX/OVX animals, OT gene expression was reduced to values equivalent to controls when T3 was given together with EB. Particular subdivisions of the PVN responded differentially to T3 and EB treatment, demonstrating marked heterogeneity of OT-containing neurons in this nucleus. Thus, parallel to and perhaps related to the manner in which thyroid hormones reduced estrogen-stimulated behaviour, endogenous or exogenous thyroid hormones interfered with estrogen stimulation of OT mRNA. These data demonstrate competition between nuclear proteins, transcription factors, in hypothalamic neurons.