Nuclear-receptors(核受体))培训课件.ppt

INTRACELLULAR RECEPTORS;The intracellular (nuclear) receptor superfamily Steroid hormones, thyroid hormones, retinoids and vitamin D ;Regulation of transcription activity;Intracellular signal molecules small, lipid-soluble molecules such as steroid hormones, retinoids, thyroid hormones, Vitamin D. (made from cholesterol) These molecules diffuse through plasma and nuclear membranes and interact directly with the transcription factors they control.;*;*;Steroid Hormones;;BIOSYNTHESIS OF STEROIDS;Endocrine disruption;Toxicants interact with hormonal system at different levels;biosynthesis and release of hormones;Mechanisms of steroid hormones signalling disruption;Endocrine disrupters in the environment?;ESTROGEN RECEPTOR – ERthe most studied target of EDCs; Estrogens: play a key role in female hormone regulation and signalling are responsible for metabolic, behavioural and morphologic changes  occurring during stages of reproduction are involved in the growth, development and homeostasis of a number of  tissues control the bone formation, regulation of homeostasis,  cardiovascular system and behaviour regulate production, transport and concentration of testicular liquid and  anabolic activity of androgens in males Synthesis in ovaries DISRUPTION - investigated in aquatic biota laboratory organisms (see notes on EDCs);ESTROGEN RECEPTORS - ER-? ER-?: subtype: ER-? (in breast, ovary, brain, liver, bone and cardiovascular system,  adrenals, testis and urogenital tract) ER-? (in kidneys, prostate and gastrointestinal tract) (ER-? in fish) ;Natural products genistein naringenin coumestrol zearalenone;Exoestrogens - Relative Potencies to bind to ERa (REPs);Toxicity assessment  number of in vivo and in vitro methods;In vitro assays;;ER- mediated effects luciferase reporter assay ;In vivo assays;Kidd, K.A. et al. 2007. Collapse of a fish population following exposure to a synthetic estro