John J. Kopchick, Ph.D.

     An understanding of the molecular basis of growth hormone (GH) action is important since GH is currently used as a human therapeutic and as a milk production enhancer  in animals.  The long term goal of my laboratory is to identify in signaling intermediates in GH responsive tissue in vivo.  An approach toward this problem has been to generate transgenic mice (see Figure) that express GH or GH antagonists, a new class of human therapeutics discovered in our laborator.  We also use a gene disruption approach.  In this case we have "knocked" out the GH receptor gene.  The resulting animals are dwarf. Using these models, we evaluate biochemical, endocrine, and physiological properties of these animals and identify signaling intermediates in GH responsive tissue. Also, we use these animal to determine the combined effects of GH and GH antagonists in diabetes induced end organ damage.  We have recently shown that GH antagonists protect mice from diabetes induced nephropathy.

Selected References:

• Li, Yunsheng, Kelder, Bruce, and Kopchick, J.J., Identification, Isolation, and Cloning of Growth Hormone (GH)-Induced Interscapular Brown Adipose Complementary Deoxyribonucleic Acid from GH Antagonist Mice.  Endocrinology, 142:2937-2945,2001.

• Okada, S. and Kopchick, J.J.  Biological effects of growth hormone and its antagonist. Trends in Molecular Medicine, 7:3:126-132, 2001.

• Chandrashekar, V., Bartke, A., Awoniyi, C.A., Tsai-Morris, C.H., Dufau, M.L., Russell, L.D. and Kopchick, J.J.  Testicular Endocrine Function in GH Receptor Gene Disrupted Mice. Endocrinology, 142(8):3443-3450, 2001.

• Coschigano, K.T., Clemmons, D., Bellush, L.L. and Kopchick, J.J.  Assessment of Growth Parameters and Life Span of GHR/BP Gene-Disrupted Mice.  Endocrinology, 141:2608-2613, 2000.

• Bellush, L.L., Doublier, S., Holland, A.N., Striker, L.J., Striker, G.E. and Kopchick, J.J.  Protection against diabetes-induced nephropathy in growth hormone receptor/binding protein gene-disrupted mice.  Endocrinology, 141:1:163-168, 2000.

• Ruan, W., Powell-Braxton, L., Kopchick, J.J. and Kleinberg, D.L.: Evidence that insulin-like growth factor I and growth hormone are required for prostate gland development. Endocrinology, 140:5:1984-1989, 1999.

• Flyvbjerg, A., Bennett, W.F., Rasch, R., Kopchick, J.J. and Scarlett, J.A.: Inhibitory effect of a growth hormone receptor antagonist (G120K-PEG) on renal enlargement, glomerular hypertrophy, and urinary albumin excretion in experimental diabetes in mice. Diabetes, 40:377-382, 1999.

• Kopchick, J.J., Chen, X.Z., Li, Y., Steger, R.W., Yun, J.S., Wagner, T.E. and Bartke, A.  Differential in vivo activities of bovine growth hormone analogues. Transgenic Research, 7:61-71, 1998.