Bali, U., Phillips, T., Hunt, H., and Unitt,\u00a0J.<\/p>\n
J Clin Endocrinol Metab.<\/span>\u00a02016 Nov;101(11):4305-4312<\/p>\n Context:<\/strong> Endogenous Cushing\u2019s syndrome is caused by chronically elevated levels of cortisol. Mifepristone,\u00a0a Glucocorticoid Receptor (GR) antagonist, is approved for the treatment of Cushing\u2019s Objective:<\/strong> To develop a qPCR assay for FKBP5 mRNA expression in blood and apply it to measure the inhibition of glucocorticoid-induced FKBP5 expression by GR antagonists in healthy human Methods:<\/strong> Briefly: blood samples were acquired from a phase I study in which healthy human subjects were administered either (a) a single dose of the GR agonist prednisone with and without Setting:<\/strong> Quotient Clinical, Nottingham, UK.<\/p>\n Results:<\/strong> Oral administration of the glucocorticoid prednisone to healthy human subjects resulted in a time-dependent increase of FKBP5 mRNA to peak levels of ~12-fold compared with unstimulated levels within 4 hours of steroid administration, followed by a reduction to baseline levels within 24 hours. Furthermore, oral administration of mifepristone or the selective GR antagonist CORT125134 had the desired effect of inhibiting prednisone-mediated activation of GR as seen by a reduction of FKBP5 mRNA levels.<\/p>\n Conclusions:<\/strong> The inhibition of FKBP5 mRNA expression by a selective GR antagonist is a potential clinical biomarker of GR antagonism.<\/p>\n","protected":false},"excerpt":{"rendered":" Developing a qPCR assay to monitor mifepristone’s effectiveness in Cushing’s syndrome patients.<\/p>\n","protected":false},"featured_media":0,"template":"","category":[1],"resource_tag":[],"class_list":["post-2416","journal-paper","type-journal-paper","status-publish","hentry","category-uncategorized"],"acf":[],"yoast_head":"\n
\nsyndrome. Currently, there is an unmet clinical need for a direct biochemical method for monitoring the immediate effectiveness of mifepristone in patients with Cushing\u2019s syndrome. The glucocorticoid induction of FK506-binding protein 5 (FKBP5) expression is rapid and has been shown to be attenuated by GR antagonists in a range of in vitro and in vivo models.<\/p>\n
\nsubjects.<\/p>\n
\nco-administration of a single oral dose of mifepristone or CORT125134 or (b) multiple daily doses of CORT125134 over 14 days with co-administration of prednisone with the final dose. FKBP5
\nmRNA levels were analyzed by qPCR in blood samples collected at selected time points.<\/p>\n