Local overexpression of GH and GH/IGF1 effects in the adult mouse hippocampus.
GH therapy improves hippocampal functions mainly via circulating IGF1. However, the roles of local GH and IGF1 expression are not well understood. We investigated whether transgenic (TG) overexpression in the adult brain of bovine GH (bGH) under the control of the glial fibrillary acidic protein (GFAP) promoter affected cellular proliferation and the expression of transcripts known to be induced by systemic GH in the hippocampus. Cellular proliferation was examined by 5-bromo-2'-deoxyuridine immunohistochemistry. Quantitative PCR and western blots were performed. Although robustly expressed, bGH-Tg did not increase either cell proliferation or survival. However, bGH-Tg modestly increased Igf1 and Gfap mRNAs, whereas other GH-associated transcripts were unaffected, i.e. the GH receptor (Ghr), IGF1 receptor (Igf1r), 2',3'-cyclic nucleotide 3'-phosphodiesterase (Cnp), ionotropic glutamate receptor 2a (Nr2a (Grin2a)), opioid receptor delta (Dor), synapse-associated protein 90/postsynaptic density-95-associated protein (Sapap2 (Dlgap2)), haemoglobin beta (Hbb) and glutamine synthetase (Gs (Glul)). However, IGF1R was correlated with the expression of Dor, Nr2a, Sapap2, Gs and Gfap. In summary, although local bGH expression was robust, it activated local IGF1 very modestly, which is probably the reason for the low response of previous GH-associated response parameters. This would, in turn, indicate that hippocampal GH is less important than endocrine GH. However, as most transcripts were correlated with the expression of IGF1R, there is still a possibility for endogenous circulating or local GH to act via IGF1R signalling. Possible reasons for the relative bio-inactivity of bGH include the bell-shaped dose-response curve and cell-specific expression of bGH.
Laboratory of Experimental Endocrinology, Department of Internal Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gröna Stråket Göteborg, Sweden.
Marion
M
Walser
Maria Teresa
MT
Samà
Ruth
R
Wickelgren
Maria
M
Aberg
Mohammad
M
Bohlooly-Y
Bob
B
Olsson
Jan
J
Törnell
Jörgen
J
Isgaard
N David
ND
Aberg
D000818:Animals; D001835:Body Weight; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000502:physiology*; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009929:Organ Size; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1