Growth Hormone (GH) and the Cardiovascular System: Studies in Bovine GH Transgenic and Inducible, Cardiac-Specific GH Receptor Gene Disrupted Mice.

摘要

Growth hormone (GH) and insulin-like growth factor I (IGF-I) are thought to play key roles in the development and maintenance of the heart. Evidence of the profound effect GH has on the heart can be found in patients with diseases that disrupt GH action. In pathological states of acromegaly (caused by oversecretion of GH), GH deficiency, and Laron Syndrome (a disease caused by mutations in the GH receptor resulting in systemic lack of GH induced action), patients exhibit unique cardiovascular phenotypes of altered structure and function. Despite these observations, the exact role of GH in the cardiovascular system is not well characterized. To better understand the effects that GH action has on the cardiovascular system, we studied the well-established bovine GH (bGH) transgenic mouse and developed a novel tamoxifen-inducible, cardiac-specific GH receptor (GHR) gene disrupted mouse (iC-GHRKO). We find that the bGH mice exhibit an age-dependent elevation of systolic blood pressure that is correlated with changes in both the brain natriuretic peptide and renin angiotensin systems. Our initial characterization of the iC-GHRKO mice surprisingly reveals that cardiac GH signaling is not necessary for maintenance of baseline cardiac function, but does appear to be required for normal glucose homeostasis in older mice. These studies take us a step closer to understanding the role of GH in the cardiovascular system and imply complex hormonal regulation of both cardiovascular function and whole body metabolism.