By S. A. Johnsen, S. Kangaspeska, G. Reid, F. Gannon (auth.), K. S. Korach, T. Wintermantel (eds.)
Nuclear hormone receptors are usually not simply vital drug goals, yet have additionally been the point of interest of a long time of energetic and hugely insightful examine. Ten years in the past, a evaluate on nuclear receptors was once entitled “The moment Decade” and a different factor of Molecular Endocrinology in 2005 handled the result of those learn efforts. The consensus from nuclear receptor learn was once after all that the signaling pathways mediated by means of those receptors warrant extra learn, even if in precept they seemed to characterize the main quick, doubtless easy signaling pathway from hormone (ligand) binding to gene expression alterations. In nuclear receptor molecular biology, estrogen receptor examine has extra specific aspects: because the discovery of ethinyl estradiol via Inhoffen and Hohlweg within the laboratories of Schering AG within the 1930s—and hence numerous many years longer than nuclear receptor - searchitself—estrogenreceptorshavebeentargetsofwidelyused,orally administered medicines. therefore, gathering scientific adventure on estrogen motion in vivo is helping to aid the growth in molecular organic research.
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Extra resources for Tissue-Specific Estrogen Action: Novel Mechanisms, Novel Ligands, Novel Therapies
Sample text
These mice are fertile and show no overt phenotype. M. Wintermantel et al. 34 to the ERα knock-out mice, which are obese (Ohlsson et al. 2000), liver-specific ERα knock-out mice do not develop obesity, nor do they show any histopathological alteration in livers of either male or female mutants. Whereas the reaction of liver-specific ERα knock-out mice to metabolic stimuli or stress remains to be investigated, this mouse line demonstrates that, under basal conditions, hepatic estrogen receptor α does not play a critical role in body weight regulation, or, in other words, that the lack of ERα action in liver does not specifically contribute to the obese phenotype of the ERαKO mouse.
Determining the specific mechanisms and ER forms mediating the effects will then provide new therapeutic approaches for expanding the development of ER-selective agonists and antagonists to produce more effective treatments. References Babiker FA, Lips D, Meyer R et al. (2006) Estrogen receptor beta protects the murine heart against left ventricular hypertrophy. Arterioscler Thromb Vasc Biol 26:1524–1530 Bae S, Zhang L (2005) Gender differences in cardioprotection against ischemia/ reperfusion injury in adult rat hearts: focus on Akt and protein kinase C signaling.
53 55 55 56 57 58 59 60 61 62 Abstract. Models of estrogen insufficiency have revealed new and unexpected roles for estrogens in males as well as females. These models include natural mutations in the aromatase gene in humans, as well as mouse knock-outs of aromatase and the estrogen receptors, and one man with a mutation in the ERα gene. These mutations, both natural and experimental, have revealed that estrogen deficiency results in a spectrum of symptoms. R. E. Jones syndrome in both males and females, with truncal adiposity and male-specific hepatic steatosis.