Abstract
Growth hormone (GH) signaling plays a key role in mediating growth, development, metabolism, and lifespan regulation. However, the mechanisms of longevity regulation at the cellular and molecular level are still not well-understood. An important area in the field of GH research is in the development of advanced transgenic systems for conditional expression of GH signaling in a cell type- or tissue-specific manner. There have been many recent studies conducted to examine the effects of tissue-specific GHR disruption. This review updates our previous discussions on this topic and summarizes recent data on the newly-made tissue-specific GHR-KO mice including intestinal epithelial cells, bone, hematopoietic stem cells, cardiac myocytes, and specific brain regions. The data from these new genetically-engineered mice have a significant impact on our understanding of the local GH signaling function.
Highlights
Growth hormone (GH) is a major regulator of growth and development of an organism and the disruption of GH signaling has shown delay the aging process and associated diseases in mice
In order the better understand the direct effects of GH in tissues numerous tissue-specific GH receptor (GHR)-KO mouse models have been developed utilizing the Cre-loxP system
In the new study conducted from the same group [9], AdGHRKO mice had increased adipocyte size and mass along with increased adipose depot size, but there was no change in the total body weight
Summary
Growth hormone (GH) is a major regulator of growth and development of an organism and the disruption of GH signaling (and subsequent IGF-1 disruption) has shown delay the aging process and associated diseases in mice. In human patients with mutations in GHR gene, there is evidence of protection against cancer and diabetes [1, 2]. This highlights the importance of studying GH’s actions in a tissue-specific manner in order to decipher the mechanism for increased longevity in mice. Since there have been several reports on mutant mice with novel tissue-specific GH signaling These studies have provided new insights on GH’s effects in different tissues. In this updated review we provide a summary of the major results from the most recent tissue-specific GHR knockout mouse studies
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