the estrogen-related receptor alpha upregulates secretin expressions in response to hypertonicity and angiotensin ii stimulationestrogen-related受体α上调分泌素表达过度紧张和血管紧张素ⅱ的刺激.pdfVIP

The Estrogen-Related Receptor Alpha Upregulates Secretin Expressions in Response to Hypertonicity and Angiotensin II Stimulation 1 1 2 1 1 Vien H. Y. Lee , Ian P. Y. Lam , Hueng-Sik Choi , Billy K. C. Chow , Leo T. O. Lee * 1 School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China, 2 Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea Abstract Osmoregulation via maintenance of water and salt homeostasis is a vital process. In the brain, a functional secretin (SCT) and secretin receptor (SCTR) axis has recently been shown to mediate central actions of angiotensin II (ANGII), including initiation of water intake and stimulation of vasopressin (VP) expression and release. In this report, we provide evidence that estrogen-related receptor a (ERRa, NR3B1), a transcription factor mainly involved in metabolism, acts as an upstream activator of the SCT gene. In vitro studies using mouse hypothalamic cell line N-42 show that ERRa upregulates SCT promoter and gene expression. More importantly, knockdown of endogenous ERRa abolishes SCT promoter activation in response to hypertonic and ANGII stimulations. In mouse brain, ERRa coexpresses with SCT in various osmoregulatory brain regions, including the lamina terminalis and the paraventricular nucleus of the hypothalamus, and its expression is induced by hyperosmotic and ANGII treatments. Based on our data, we propose that both the upregulation of ERRa and/or the increased binding of ERRa to the mouse SCT promoter are two possible mechanisms for the elevated SCT expression upon hyperosmolality and central ANGII stimulat