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N Aberg, Department of Internal Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, SE-413 45, Sweden
I Johansson, Department of Internal Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
M Aberg, Center of Brain Research and Rehabilitation, Institute of Physiology and Neuroscience, University of Gothenburg, Gothenburg, Sweden
J Lind, Center of Brain Research and Rehabilitation, Institute of Physiology and Neuroscience, University of Gothenburg, Gothenburg, Sweden
U Johansson, Department of Internal Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
C Cooper-Kuhn, Center of Brain Research and Rehabilitation, Institute of Physiology and Neuroscience, University of Gothenburg, Gothenburg, Sweden
H Kuhn, Center of Brain Research and Rehabilitation, Institute of Physiology and Neuroscience, University of Gothenburg, Gothenburg, Sweden
J Isgaard, Department of Internal Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

Correspondence: N. David Aberg, Email: david.aberg{at}medic.gu.se

Abstract

IGF-I treatment has been shown to enhance cell genesis in the brains of adult GH- and IGF-I-deficient rodents; however, the influence of GH therapy remains poorly understood. The present study investigated the effects of peripheral recombinant bovine GH (bGH) on cellular proliferation and survival in the neurogenic regions (subventricular zone, SVZ, and dentate gyrus of the hippocampus), as well as the corpus callosum, striatum, parietal cortex, and piriform cortex. Hypopituitarism was induced in female rats by hypophysectomy, and the rats were supplemented with thyroxine and cortisone acetate. Subsequently, the rats received daily subcutaneous injections of bGH for either 6 or 28 days, respectively. Following 5 days of peripheral bGH administration, the number of bromodeoxyuridine (BrdU)-positive cells was increased in the hippocampus, striatum, parietal cortex, and piriform cortex after 6 and 28 days. In the SVZ, however, BrdU-positive cells increased only after 28 days of bGH treatment. No significant change was observed in the corpus callosum. In the hippocampus, after 28 days of bGH treatment, the number of BrdU/NeuN-positive cells was increased proportionally to increased number of BrdU-positive cells. 3H-thymidine incorporation in vitro revealed that 24 hours of bGH exposure was sufficient to increase cell proliferation in adult hippocampal progenitor cells.

This study shows for the first time that 1) peripheral bGH administration increased the number of newborn cells in the adult brain and 2) bGH exerted a direct proliferative effect on neuronal progenitor cells in vitro.