All ETDs from UAB

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.

Share

COinS