PHYSIOLOGY AND PATHOPHYSIOLOGY OF GROWTH HORMONE VARIANT

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DESCRIPTION (provided by applicant): Candidate and Environment: Susan E. Kirk, M.D. is a well-trained clinician whose application for a Mentored Clinical Scientist Development Award will provide the opportunity for her to expand her clinical and basic science research skills. Currently, she is an Assistant Professor in Internal Medicine at the University of Virginia. In addition to her own laboratory, Dr. Kirk has the support and use of the laboratories of Dr. Eugene Barrett (Director, Diabetes Education Research Center) and Dr. Michael Thorner (Chair, Department of Medicine). In addition, the University of Virginia maintains an excellent, state-of-the-art General Clinical Research Center for completion of clinical studies. Background: During Pregnancy, the normal placenta produces multiple hormones including human chorionic somatomammotropin (hCS, formerly termed human placental lactogen or hPL) and another member of the growth hormone gene family -- placental growth hormone variant or GH-V. Because hCS circulates at high concentrations and has approximately 85 percent homology to pituitary growth hormone (GH), many of the GH-like biologic effects seen with pregnant Type I diabetic woman (worsening of microvascular disease), are attributed to the GH- like properties of hCS. The major hypothesis of this proposal is the GH-V, not hCS, is the principal somatotropic agent present in normal pregnancy. It, like pituitary GH, can a) influence pituitary secretion, b) stimulate GH receptor signaling, c) accelerate microvascular changes of diabetes, and d) may play a role in determining intrauterine growth in normal pregnancy and pregnancy complicated by diabetes mellitus. Research Plan: will measure 1) the impact of GH-V on pituitary GH secretion in rats; 2) signal transduction pathways activated by GH-V; 3) the effect of GH-V on glomerular structure in mice.