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Pharm Sci Seminar – John Kopchick, PhD

March 15 @ 12:00 PM - 12:50 PM

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John Kopchick, PhD
Goll-Ohio Eminent Scholar
Professor, Molecular Biology
Ohio University

Host: Dean Swanson

Growth Hormone, Mini-mice, Football, Dirty Shorts, and a new Drug

Employing a structure/function approach to the understanding of the molecular topology of growth hormone (GH), we discovered that glycine (Gly) 119 of bovine GH and Gly 120 of human GH were important amino acids required for GH activity.  Substitution of this Gly residue with a variety of amino acids resulted in molecules that lacked growth-promoting activity.  More importantly, these molecules inhibited the actions of GH both in vitro and in vivo.  These results were the basis for the discovery of GH Receptor Antagonists.  Since that time, we have focused our attention on establishing the mechanism by which they inhibit GH action. An update of that data will be presented.

In vitro, GH antagonists (bGH-G119K or hGH-G120K) inhibit GH-mediated differentiation of 3T3F422A preadipocytes to adipocytes.  Using this same cell system, we also have shown that GH antagonists inhibit the anti-insulin actions of GH. Thus, GH antagonists are potent insulin sensitizers.

Expression of GH antagonist genes in transgenic mice results in dwarf animals. These mice are protected against diabetes-induced glomerulosclerosis and ischemia-induced retinal neovascularization. Additionally, injection of GH antagonists into diabetic mice inhibits kidney enlargement, glomerular hypertrophy, and urinary albumin excretion.

Together, these results laid the foundation for the clinical use of GH antagonists when endogenous GH levels are elevated or when GH is a factor in the progression of a clinically important disorders.  Three such indications are acromegaly, diabetes induced end organ damage, and certain types of cancer.  The GH antagonist, SOMAVERT TM (Pegvisomant for Injection), has been approved for use in acromegalic individuals.  An update on this data will be given. Additionally, data as it relates to mice in which the GH Receptor gene has been disrupted will be presented as a function of longevity.

Details

Date:
March 15
Time:
12:00 PM - 12:50 PM
Event Category:

Venue

1116 Rennebohm Hall
777 Highland Ave
Madison, WI 53705 United States
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Website:
https://pharmacy.wisc.edu/about/rennebohm-hall/

Organizer

Pharmaceutical Sciences Division
Phone:
608-262-0353
Website:
https://pharmacy.wisc.edu/psd

Other

Speaker
John Kopchick, PhD
Presentation Title
Growth Hormone, Mini-mice, Football, Dirty Shorts, and a new Drug