Principal Investigator/Program Director (Last, first, middle): Waxman, David, J RESEARCH &RELATED Other Project Information 1. * Are Human Subjects Involved? m Yes l No 1.a. If YES to Human Subjects Is the IRB review Pending? m Yes m No IRB Approval Date: Exemption Number: 1 2 3 4 5 6 Human Subject Assurance Number 2. * Are Vertebrate Animals Used? l Yes m No 2.a. If YES to Vertebrate Animals Is the IACUC review Pending? m Yes l No IACUC Approval Date: 03-22-2006 Animal Welfare Assurance Number A3522-01 3. * Is proprietary/privileged information m Yes l No included in the application? 4.a.* Does this project have an actual or potential impact on m Yes l No the environment? 4.b. If yes, please explain: 4.c. If this project has an actual or potential impact on the environment, has an exemption been authorized or an environmental assessment (EA) or environmental impact statement (EIS) been performed? m Yes m No 4.d. If yes, please explain: 5.a.* Does this project involve activities outside the U.S. or m Yes l No partnership with International Collaborators? 5.b. If yes, identify countries: 5.c. Optional Explanation: 6. * Project Summary/Abstract 1984-Abstract.pdf Mime Type: application/pdf 7. * Project Narrative 5965-Narrative.pdf Mime Type: application/pdf 8. Bibliography &References Cited 7657-2Bibliography.pdf Mime Type: application/pdf 9. Facilities &Other Resources 477-Facilities.pdf Mime Type: application/pdf 10. Equipment 1755-Equipment.pdf Mime Type: application/pdf 11. Other Attachments 6793-LAB_DK_CVs.pdf Mime Type: application/pdf Tracking Number: Other Information Page 5 OMB Number: 4040-0001 Expiration Date: 04/30/2008 Principal Investigator/Program Director (Last, first, middle): Waxman, David, J 6. Project Summary/Abstract The long-range goal of this project is to elucidate the endocrine regulation of hepatic cytochromes P450 (Cyps) and other enzymes that metabolize steroid hormones, bile acids, drugs, carcinogens and other lipophilic substrates of medical or environmental importance, with a focus on the actions of growth hormone (GH), a pituitary polypeptide hormone. The proposed project period uses the mouse as a model system to investigate the molecular mechanisms by which GH and its sex-dependent ultradian secretory patterns regulate Cyps and many other liver-expressed genes in a sex-specific manner. The major objective of this project is to elucidate the mechanisms that underpin the dependence of sex-specific liver gene expression on STAT5b, a signal transducer and activator of transcription that is directly activated by each incoming adult male plasma GH pulse, and on HNF4?, a liver-enriched transcription factor. The studies proposed will test the hypothesis that the actions of STAT5b and HNF4? on sex-specific Cyps and other GH pulse-responsive genes involve both direct and indirect mechanisms operating through a complex regulatory network. Genome-wide approaches will be used to elucidate
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