| 摘要 |
This invention relates to oxysteroids and oxysteroid hormones which have been identified. These oxysteroids are C27 modified sterols, particularly derivatives of intermediates in cholesterol synthesis, including lanosterol, zymosterol and desmosterol, including C27 diol and C27 acid derivatives, as well as related compounds and analogs thereof. The oxysteroids are capable of binding to or otherwise interacting with orphan nuclear receptors to result in modulation of gene expression. The invention further relates to methods of modulating the rate of cholesterol synthesis in a mammal. More specifically, the invention relates to treatment of cholesterol-related conditions which are improved or ameliorated by modulating the rate of cholesterol synthesis or cholesterol metabolism in a human in need thereof by administration of these oxysteroids, analogs or antagonists thereof. The invention includes methods for ameliorating, treating or preventing macular degeneration in a mammal comprising administering to said mammal an agent which stimulates or enhances the expression or activity of steroid sulphotransferase (SLUT2), particularly SLUT2B1b, or which stimulates or enhances the expression or activity of CYP27A1 or sterol 27-hydroxylase or otherwise increasing the sulfonation or 27-hydroxylation of cholesterol intermediates, including 7-ketocholesterol. Assays for identification of analogs, antagonists or modulators of these oxysteroids or of sterol 27-hydroxylase are also provided.
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