Somponpun Suwit J, Sladek Celia D
Department of Physiology and Biophysics, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
J Neurosci. 2003 May 15;23(10):4261-9. doi: 10.1523/JNEUROSCI.23-10-04261.2003.
The vasopressin (VP) magnocellular neurosecretory cells (MNCs) in the supraoptic and paraventricular (PVN) nuclei are regulated by estrogen and exhibit robust expression of estrogen receptor (ER)-beta. In contrast, only approximately 7.5% of oxytocin (OT) MNCs express ER-beta. We examined the osmotic regulation of ER-beta mRNA expression in MNCs using quantitative in situ hybridization histochemistry. Hyper-osmolality induced via 2% hypertonic saline ingestion significantly decreased, whereas sustained hypo-osmolality induced via d-d-arginine VP and liquid diet increased ER-beta mRNA expression in MNCs (p < 0.05). Thus, the expression of ER-beta mRNA correlated inversely with changes in plasma osmolality. Because hyper-osmolality is a potent stimulus for VP and OT release, this suggests an inhibitory role for ER-beta in MNCs. Immunocytochemistry demonstrated that the decrease in ER-beta mRNA was translated into depletion of receptor protein content in hyper-osmotic animals. Numerous MNCs were positive for ER-beta in control animals, but they were virtually devoid of ER-beta-immunoreactivity (IR) in hyper-osmotic animals. The osmotically induced decrease in ER-beta expression was selective for MNCs because ER-beta-IR remained unaltered in PVN parvocellular neurons. Plasma estradiol and testosterone were not correlated with ER-beta mRNA expression after osmotic manipulation, suggesting that ER-beta expression was not driven by ligand availability. Expression of FOS-IR in MNCs with attenuated ER-beta-IR, and the absence of FOS-IR in parvocellular neurons that retain ER-beta-IR suggest a role for neuronal activation in the regulation of ER-beta expression in MNCs. Thus, osmotic modulation of ER-beta expression in MNCs may augment or attenuate an inhibitory effect of gonadal steroids on VP release.
视上核和室旁核中的血管加压素(VP)大细胞神经分泌细胞(MNCs)受雌激素调节,并表现出雌激素受体(ER)-β的强烈表达。相比之下,只有约7.5%的催产素(OT)MNCs表达ER-β。我们使用定量原位杂交组织化学方法研究了MNCs中ER-β mRNA表达的渗透压调节。通过摄入2%高渗盐水诱导的高渗状态显著降低了ER-β mRNA的表达,而通过d-d-精氨酸加压素和流食诱导的持续低渗状态则增加了MNCs中ER-β mRNA的表达(p<0.05)。因此,ER-β mRNA的表达与血浆渗透压的变化呈负相关。由于高渗是VP和OT释放的有力刺激因素,这表明ER-β在MNCs中具有抑制作用。免疫细胞化学显示,在高渗动物中,ER-β mRNA的减少转化为受体蛋白含量的减少。在对照动物中,许多MNCs对ER-β呈阳性,但在高渗动物中它们几乎没有ER-β免疫反应性(IR)。渗透压诱导的ER-β表达下降对MNCs具有选择性,因为在室旁核小细胞神经元中ER-β-IR保持不变。渗透压操作后,血浆雌二醇和睾酮与ER-β mRNA表达无关,这表明ER-β的表达不是由配体可用性驱动的。ER-β-IR减弱的MNCs中FOS-IR的表达,以及保留ER-β-IR的小细胞神经元中没有FOS-IR,这表明神经元激活在MNCs中ER-β表达的调节中起作用。因此,MNCs中ER-β表达的渗透压调节可能增强或减弱性腺类固醇对VP释放的抑制作用。