RT Journal Article SR Electronic T1 Identification of the First Synthetic Steroidogenic Factor 1 Inverse Agonists: Pharmacological Modulation of Steroidogenic Enzymes JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 900 OP 908 DO 10.1124/mol.107.040089 VO 73 IS 3 A1 Del Tredici, Andria L. A1 Andersen, Carsten B. A1 Currier, Erika A. A1 Ohrmund, Steven R. A1 Fairbain, Luke C. A1 Lund, Birgitte W. A1 Nash, Norman A1 Olsson, Roger A1 Piu, Fabrice YR 2008 UL http://molpharm.aspetjournals.org/content/73/3/900.abstract AB Steroidogenic factor SF-1, a constitutively active nuclear hormone receptor, is essential to the development of adrenal and gonadal glands and acts as a shaping factor of sexual determination and differentiation. Its effects are exerted primarily through the control of the synthesis of steroid hormones. The functional cell-based assay Receptor Selection and Amplification Technology (R-SAT) was used to identify potent and selective SF-1 inverse agonists through the screening of a chemical library of drug-like small-molecule entities. Among them, 4-(heptyloxy)phenol (AC-45594), a prototype inverse agonist lead, was used to show that SF-1 constitutive activity can be pharmacologically modulated by a synthetic ligand. In a physiological system of endocrine function, the expression of several reported SF-1 target genes, including SF-1 itself, was inhibited by treatment with AC-45594 and analogs. Thus, pharmacological modulation of SF-1 is critical to its function as an endocrine master regulator and has potentially important consequences to diseases in which SF-1 activity is critical. The American Society for Pharmacology and Experimental Therapeutics