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Proliferative and protective effects of the GH/IGF-I axis on cardiomyocytes and neural progenitor cells

Sammanfattning
Cardiovascular disease is the most common cause of mortality in the Western world and the majority of cardiovascular deaths are caused by coronary artery disease or cerebrovascular disease. Growth hormone (GH) is a growth-promoting hormone synthesized by the pituitary. Most of the effects of GH are mediated by local- or liver-produced insulin-like growth factor-I (IGF-I) but GH receptors have been found in a number of extra-hepatic tissues, suggesting direct, IGF-I-independent effects of GH. Synthetic and endogenous GH secretagogues (GHS) release GH from the pituitary and may also exert direct effects in various tissues. Recent data suggest the GH/IGF-I system to improve cardiac performance and to be tissue protective after myocardial infarction. In the brain, the activity of the GH/IGF-I axis has been suggested to improve cognitive function, to exert cell protection after ischemic injury and to stimulate neurogenesis. The aim of this thesis was to investigate direct proliferative and protective effects of compounds of the GH/IGF-I axis on cells or tissue from organs that are exposed to ischemic injury or degenerative disease, such as heart and brain. . Our results suggest that the GH/IGF-I axis is involved in the generation of new cells, both in the heart and in the brain, and that some of these effects are independent of IGF-I. More specifically, the synthetic GHS hexarelin and the endogenous GHS ghrelin were found to have proliferative effects both in rat cardiomyocyte-like cells and in adult rat hippocampal progenitor (AHP) cells in vitro. In addition, hexarelin exerted protective effects in AHP cells after induction of apoptosis. Furthermore, peripheral administration of bovine GH (bGH) to hypophysectomized rats in vivo had proliferative effects in several brain regions and a proliferative effect was also found when AHP cells were incubated with bGH in vitro. The results in this thesis may have potentially important clinical implications in ischemic and degenerative cardiac and cerebral disease, when cell protection and recruitment of new cells are desirable. Keywords: GH, IGF-I, GH secretagogues, ghrelin, cardiovascular, neurogenesis, hippocampus, proliferation, protection
Delarbeten
I. I. Pettersson, G. Muccioli, R. Granata, R Deghenghi, E. Ghigo, C Ohlsson, J. Isgaard. Natural (Ghrelin) and Synthetic (Hexarelin) Growth Hormone Secretagogues Stimulate H9c2 Cardiomyocyte Cell Proliferation. Journal of Endocrinology (2002) Vol 175: 201-209. ::pmid::12379504
 
II. I. Johansson, S. Destefanis, N. D. Åberg, M.A.I. Åberg, K. Blomgren, C. Zhu, C. Ghe, R. Granata, E. Ghigo, G. Muccioli, P.S. Eriksson and J. Isgaard. Proliferative and Protective effects of Growth Hormone Secretagogues on Adult Rat Hippocampal Progenitor cells. Endocrinology (2008) Vol 149(5): 2191-2199. ::pmid::18218693
 
III. N. David Åberg, Inger Johansson, Maria A. I. Åberg, Johan Lind, Ulf Johansson, Christiana M. Cooper-Kuhn, Fred H. Gage, H Georg Kuhn, Jörgen Isgaard. Peripheral Administration of GH Induces Cell Proliferation in the Adult Hypophysectomized Rat Brain. Manuscript.
 
Examinationsnivå
Doctor of Philosophy (Medicine)
Universitet
University of Gothenburg. Sahlgrenska Academy
Institution
Inst of Medicine. Dept of Internal Medicine
E-post
inger_johansson@live.se
URL:
http://hdl.handle.net/2077/10123
Samlingar
  • Doctoral Theses / Doktorsavhandlingar Institutionen för medicin
  • Doctoral Theses from Sahlgrenska Academy
  • Doctoral Theses from University of Gothenburg / Doktorsavhandlingar från Göteborgs universitet
Fil(er)
Thesis frame (6.535Mb)
Abstract (142.8Kb)
Datum
2008-05-15
Författare
Johansson, Inger
Nyckelord
GH
IGF-I
GH secretagogues
Ghrelin
Cardiovascular
Neurogenesis
Hippocampus
Proliferation
Protection
Publikationstyp
Doctoral thesis
ISBN
978-91-628-7490-2
Språk
eng
Metadata
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