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The exon 3-deleted isoform of the growth hormone receptor mRNA is present in ovine choroid plexus
Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Article in journal (Refereed) Submitted
URN: urn:nbn:se:uu:diva-92528OAI: oai:DiVA.org:uu-92528DiVA: diva2:165646
Available from: 2005-01-20 Created: 2005-01-20Bibliographically approved
In thesis
1. CNS Targets for GH and IGF-1: Emphasis on Their Regulation in Relation to Cognitive Processes
Open this publication in new window or tab >>CNS Targets for GH and IGF-1: Emphasis on Their Regulation in Relation to Cognitive Processes
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The interest for the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and its role in the central nervous system (CNS) has grown during the past decade. GH has been associated with psychological functions as sleep, mood, general well-being and learning and memory. The present thesis is a contribution to clarify the functions and mechanisms involved in the actions of GH and IGF-1 in the CNS. A variant of the GH receptor (GHR) gene transcript lacking exon 3 (GHR3-) was cloned from ovine choroid plexus epithelial cells and tissue. The GHR3- transcript has previously only been identified in human tissue. Further, an anatomical study of the localization of GHR mRNA in the rat brain stem and spinal cord was carried out by the use of in situ hybridization. High densities of GHRs were found in areas associated with the regulation of food intake, sleep and nociception, functions known to be influenced by the GH/IGF-1 axis. The interaction with the opioid system was studied by an acute treatment with morphine. The levels of the transcripts for GHR and GHBP in the rat hippocampus and spinal cord were decreased 4 h after the injection of the opiate and restored to normal levels after 24 h. Young and aged rats injected with GH or IGF-1 showed differential gene regulation of subunits of the NMDA subtype of glutamate receptor in the hippocampus. This indicates an age-related difference in the sensitivity to GH/IGF-1 mediated effects on memory functions. Moreover, hypophysectomized rats treated with GH showed improved performance in the Morris water maze, a spatial memory task. The effect was accompanied with an increase in transcripts for NMDA receptor subunits and its associated membrane anchoring PSD-95 protein. Taken together, the results suggest that GH and/or IGF-1 play important roles in mechanisms associated with cognitive functions.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 64 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 2
Pharmaceutical pharmacology, Central nervous system, Growth hormone, Insulin-like growth factor-1, Receptor mRNA regulation, N-methyl-D-aspartate receptor mRNA, Morris water maze, Farmaceutisk farmakologi
National Category
Pharmacology and Toxicology
urn:nbn:se:uu:diva-4758 (URN)91-554-6132-8 (ISBN)
Public defence
2005-02-11, B41, BMC, Husargatan 3, Uppsala, 13:15
Available from: 2005-01-20 Created: 2005-01-20Bibliographically approved

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