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Enhanced Spontaneous Locomotor Activity in Bovine GH Transgenic Mice Involves Peripheral Mechanisms

Departments of Physiology (M.B.-Y., B.O., O.B., J.T.), Oral Biochemistry (A.G.-L.), and Pharmacology (B.S.), Göteborg University, Göteborg, Sweden S-40530; Research Centre for Endocrinology and Metabolism (M.B.-Y., B.O., O.B., O.G.P.I., C.O., J.T.), Sahlgrenska Hospital, Göteborg, Sweden S-41345; and AstraZeneca Transgenic Centre (J.T.), AstraZeneca Research and Development, Mölndal, Sweden S-43183

Address all correspondence and requests for reprints to: Jan Törnell, AstraZeneca Transgenic Centre, AstraZeneca R&D, S-43183 Mölndal, Sweden. E-mail: jan.tornell{at}astrazeneca.com

Clinical and experimental studies indicate a role for GH in mechanisms related to anhedonia/hedonia, psychic energy, and reward. Recently we showed that transgenic mice with general overexpression of bovine GH display increased spontaneous locomotor activity. In the present study, we investigated whether this behavioral change is owing to a direct action of GH in the central nervous system or to peripheral GH actions. A transgenic construct, containing the glial fibrillary acidic protein promoter directing specific expression of bovine GH to the central nervous system, was designed. The central nervous system–specific expression of bovine GH in the glial fibrillary acidic protein-bovine GH transgenic mice was confirmed, but no effect on spontaneous locomotor activity was observed. Serum bovine GH levels were increased in glial fibrillary acidic protein–bovine GH transgenic mice but clearly lower than in transgenic mice with general overexpression of bovine GH. In contrast to the transgenic mice with general overexpression of bovine GH, glial fibrillary acidic protein-bovine GH mice did not display any difference in serum IGF-I levels. The levels of free T₃ and the conversion of the free T₄ to free T₃ were only increased in transgenic mice with general overexpression of bovine GH, but serum corticosterone levels were similarly increased in both transgenic models. These results suggest that free T₃ and/or IGF-I, affecting dopamine and serotonin systems in the central nervous system, may mediate the enhanced locomotor activity observed in transgenic mice with general overexpression of bovine GH.

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