Advisory Committee Chair
Stuart J Frank
Advisory Committee Members
Thomas L Clemens
Robin G Lorenz
Joseph L Messina
Rosa Serra
Anne Theibert
Document Type
Dissertation
Date of Award
2008
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) exert profound growth promoting actions during pre- and post-natal skeletal development. GH and IGF- 1 appear to cause these anabolic actions by influencing a variety of effects on osteoblast proliferation, differentiation, and survival. However, because GH stimulates the production of IGF-1 from the liver and other GH-responsive peripheral tissues, including bone, the individual contributions of these two molecules to anabolic responses in bone remains poorly defined. In this dissertation research, I sought to distinguish the direct and indirect (IGF-1 dependent) GH actions on osteoblasts. In the first section of this thesis, I employed a genetic approach to disrupt the IGF-1 receptor (IGF-1R) specifically in osteoblasts, thereby eliminating its potential contribution to GH actions. In these studies, I demonstrated that even though direct actions of GH to reduce osteoblast apoptosis can be demonstrated in vitro, the IGF-1R is required for the anabolic effects of GH on osteoblasts in vivo. In the second part of this thesis, I employed another genetic mouse model to disrupt GHR specifically in osteoblasts. The results of these studies suggest that GHR is required for the full action of IGF-1 in osteoblasts in vitro, but this deficit can be partially compensated in vivo except in areas of the highest GHR concentration, e.g. cortex.
Recommended Citation
DiGirolamo, Douglas J., "Growth Hormone Signaling and Action in Osteoblasts" (2008). All ETDs from UAB. 265.
https://digitalcommons.library.uab.edu/etd-collection/265