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Growth Hormone (GH) and the Glomerular Podocyte

Brittain, Alison Louise
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1554208861914841

Abstract Details

2019, Doctor of Philosophy (PhD), Ohio University, Molecular and Cellular Biology (Arts and Sciences).
Growth Hormone (GH) is a peptide hormone secreted from the anterior pituitary that has numerous effects on the kidney. In mice, excess GH is associated with the development of glomerular disease. The glomerulus is the most proximal part of the nephron and contains several different cell types, including the podocyte, which forms part of the filtration barrier between the blood and urine. Previous literature suggests that in vitro, GH may damage the podocyte when administered at high levels. Whether these damaging effects exist in vivo has yet to be determined and is part of the focus of this dissertation. Discussed within this work is a thorough review of the role of GH in the renal system and podocyte physiology. These chapters are followed by a study examining the effects of differing GH concentrations on mouse and human podocytes in vitro, which highlight an ability for GH to induce a moderate amount of epithelial-to-mesenchymal transition (EMT) at 50 ng/mL while reducing apoptosis and cellular viability. The next chapter of this dissertation details the characterization of a novel mouse model: the podocyte-specific GHR gene “knockdown” mouse (PodGHR-/-). The PodGHR-/- mouse was developed and studied under three conditions: the normal aging C57BL6/J phenotype, transgenic bovine (b) GH overexpression, and streptozotocin (STZ)-induced diabetes. Studies of the PodGHR-/- mouse over the course of normal aging showed detrimental changes to the kidney in male mice in the form of increased glomerular filtration rate (GFR), glomerular volume and albumin to creatinine ratio (ACR). When crossed with the bovine GH (bGH) overproducing mouse, PodGHR-/- double transgenic mice (bPodGHR-/-) exhibited decreased gene expression markers of renal damage along with decreased fluid retention, suggestive of some renoprotection. However, female bPodGHR-/- mice exhibited none of these changes but showed increased kidney hydroxyproline content at young and old age which was not associated with other markers of renal decline. When induced to diabetes with STZ, male PodGHR-/- mice did not exhibit overt changes in renal physiology, but also did not exhibit the decreases in podocyte foot process number or increases in foot process width that were seen in wild-type (WT) diabetic mice. The final study of this dissertation examined datasets to determine GH receptor (GHR) gene expression levels in chronic kidney diseases. This study concluded that GHR and insulin-like growth factor 1 (IGF1) gene expression levels are generally decreased in human and mouse models of chronic kidney disease, while IGFBP6 gene expression levels are generally increased. Cumulatively, the studies detailed in this dissertation suggest GH action through the podocyte plays a nuanced role in normal renal physiology and in the development of renal disease, being beneficial to the podocyte in some cases and detrimental in others.
John Kopchick (Advisor)
Darlene Berryman (Committee Chair)
Coshigano Karen (Committee Member)
Malgor Ramiro (Committee Member)
Menon Ram (Committee Member)
225 p.
Biology; Endocrinology; Molecular Biology
Growth hormone; kidney disease; podocyte; diabetic nephropathy; bGH nephropathy; glomerular disease; glomerulus

Recommended Citations

Citations

  • Brittain, A. L. (2019). Growth Hormone (GH) and the Glomerular Podocyte [Doctoral dissertation, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1554208861914841

    APA Style (7th edition)

  • Brittain, Alison. Growth Hormone (GH) and the Glomerular Podocyte. 2019. Ohio University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1554208861914841.

    MLA Style (8th edition)

  • Brittain, Alison. "Growth Hormone (GH) and the Glomerular Podocyte." Doctoral dissertation, Ohio University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1554208861914841

    Chicago Manual of Style (17th edition)

ohiou1554208861914841
340
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This open access ETD is published by Ohio University and OhioLINK.