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Growth Horm IGF Res. 2014 Jun 28. pii: S1096-6374(14)00052-5. doi: 10.1016/j.ghir.2014.06.004. [Epub ahead of print]

Behavioural phenotyping of male growth hormone-releasing hormone (GHRH) knockout mice.

Author information

  • 1Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
  • 2Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • 3Department of Pharmacy, G. d'Annunzio University, Chieti, Italy. Electronic address: brunetti@unich.it.



GH-releasing hormone (GHRH) is a key regulator of GH secretion. The role of GH in anxiety is somewhat contradictory. The aim of this study is to elucidate the consequences of lack of GHRH on emotional behaviour in a mouse model of GH deficiency due to removal of the GHRH gene (GHRH knock out, GHRHKO).


Homozygous GHRHKO and wild type male mice were utilized for this study. The emotional behaviour was measured through a battery of behavioural tests (locomotor activity/open field, light-dark exploration, elevated plus maze, forced swim test, tail suspension test). To correlate the emotional behaviour with brain neurochemistry, we evaluated thyrotropin-releasing hormone (TRH) gene expression in hypothalamic tissue by real-time PCR, and the levels of norepinephrine (NE), dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) in prefrontal cortex by HPLC analysis.


GHRHKO mice showed increased exploratory activity. In the open field test (P<0.005), light-dark box (P<0.005) and elevated plus maze (P<0.05), GHRHKO mice demonstrated a decrease in anxiety-related behaviour. In addition, GHRHKO mice showed reduced immobility time with respect to control in forced swim test and tail suspension test (P<0.0001). The gene expression of hypothalamic TRH (P<0.05) was increased, while NE levels in prefrontal cortex were decreased compared to control (P<0.05).


These results suggest that in male mice GHRH deficiency brings about an increased physical activity and decreased anxiety- and depression-related behaviour, possibly related to increased TRH and decreased NE levels in the brain.

Copyright © 2014 Elsevier Ltd. All rights reserved.


Anxiety; Depression; Growth hormone-releasing hormone knockout; Norepinephrine; Thyrotropin-releasing hormone

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