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Molecular Endocrinology, doi:10.1210/me.2005-0532
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Molecular Endocrinology 20 (11): 2819-2830
Copyright © 2006 by The Endocrine Society

In Vivo Imaging of Hepatic Growth Hormone Signaling

Stuart J. Frank1, Xiangdong Wang1, Kai He, Ning Yang, Peng Fang, Ron G. Rosenfeld, Vivian Hwa, Tandra R. Chaudhuri2, Luqin Deng and Kurt R. Zinn

Department of Medicine (S.J.F., X.W., K.H.), Division of Endocrinology, Diabetes, and Metabolism, Department of Cell Biology (S.J.F., N.Y., L.D.), Departments of Medicine, Division of Hematology and Oncology (K.R.Z.), and Radiology (T.R.C.) and the Laboratory for Multimodality Imaging (T.R.C., K.R.Z.), University of Alabama at Birmingham, Birmingham, Alabama 35294-0012; Endocrinology Section (S.J.F.), Medical Service, Veterans Affairs Medical Center, Birmingham, Alabama 35233; and Department of Pediatrics (P.F., R.G.R., V.H.), Oregon Health & Sciences University, Portland, Oregon 97239

Address all correspondence and requests for reprints to: Stuart J. Frank, University of Alabama at Birmingham, 1530 3rd Avenue South, BDB 861, Birmingham, Alabama 35294-0012. E-mail: sjfrank{at}uab.edu; or Kurt R. Zinn, University of Alabama at Birmingham, 1530 3rd Avenue South, BDB 802, Birmingham, Alabama 35294-0012. E-mail: kurtzinn{at}uab.edu.

We developed a system to noninvasively and repeatedly image in vivo hepatic GH signaling. GH regulates postnatal growth and metabolism. It affects numerous tissues, but has major effects in liver. We used nude mice for adenoviral-mediated delivery of a signal transducer and activator of transcription 5-dependent GH response element, a luciferase reporter to detect GH signaling pathway activation. We detected by noninvasive bioluminescence imaging GH-induced hepatic GH signaling serially within intact mice. Statistically significant effects of GH dose and time dependence were detected in the liver luciferase signal that peaked 3 h after GH injection. Codelivery of GH receptor significantly enhanced GH response, an effect that was further augmented by fasting. Our imaging system allows detailed in vivo analysis of GH signaling and action and may be a paradigm for studies of additional signaling pathways in liver and other tissues.




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