Effects and Action Mechanisms of Lipopolysaccharide-regulated Steroidogenesis in Adrenal Cortex

• Main Authors: Hsin-Lei Huang, 黃心蕾
• Other Authors: Hsiao-Fung Pu
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/39514520004572410071

博士 === 國立陽明大學 === 生理學研究所 === 98 === The relationship between immune and endocrine system is vital to maintain homeostasis in several illnesses. Toll-like receptors (TLRs), lipopolysaccharide (LPS)-regulated receptors, were found not only to mediate the inflammatory response but also to be important in the adrenal stress response. Therefore, this thesis discusses the effects of LPS on adrenal cortex response by using adrenal zona fasciculata-reticularis (ZFR) and zona glomerulosa (ZG) cells. As a result, LPS can induce the coticosterone production and steroidogenesis, such as StAR protein, LXRα and SREBP-1c in adrenal ZFR cells. Furthermore, LPS-induced corticosterone production is directly through TLR2 and TLR4 related NFκB pathway in adrenal ZFR cells. Besides, in adrenal ZG cells, TLR2 and TLR4 siRNA or blockers significantly suppress LPS-induced aldosterone production. LPS also activates NFκB, PI3K/Akt and ERK/MEK pathway to regulate aldosterone production and steroidogenesis, such as SR-B1 and StAR protein in the adrenal ZG cells. However, the clinical research further demonstrates that plasma aldosterone level dose not relate to inflammatory response in hemodialysis (HD), because the decreasing of plasma aldosterone level is the result of the body fluid overloaded. Plasma aldosterone level and the ratio of extracellular water and total body water (ECW/TBW) are also the important predictors of both all-cause mortality and cardiovascular events in HD patients.