Peri-pubertal gonadotropin-releasing hormone analog treatment affects hippocampus gene expression without changing spatial orientation in young sheep

Behav Brain Res. 2013 Apr 1:242:9-16. doi: 10.1016/j.bbr.2012.12.027. Epub 2012 Dec 22.


Background: Normal brain maturation is the result of molecular changes that can be modulated by endocrine variables associated with brain plasticity and results in sex- and age specific changes in cognitive performance. Using a sheep model, we have previously shown that peri-pubertal pharmacological blockade of gonadotropin releasing hormone (GnRH) receptors results in increased sex-differences in cognitive executive function and emotional control. In this study we explore effects of this treatment regime on hippocampal gene expression and spatial orientation.

Methods: The study was conducted with 30 same-sex twin lambs, half of which were treated with the GnRH analog (GnRHa) goserelin acetate every 4th week, beginning before puberty, until 50 weeks of age. Animals were tested in their spatial orientation ability at 48 weeks of age. Quantitative real time PCR analysis was conducted to examine effects of treatment on the expression of genes associated with synaptic plasticity and endocrine signaling.

Results: GnRHa treatment was associated with significant sex- and hemisphere specific changes in mRNA expression for some of the genes studied. The treatment had no significant effect on spatial orientation. However, there was a tendency that females performed better than males in spatial orientation.

Conclusion: Our results indicate that GnRH directly and/or indirectly, is involved in the regulation of sex- and side-specific expression patterns of genes. Hence, these results should be considered when long-term peri-pubertal GnRHa treatment is used in children.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Female
  • Functional Laterality
  • Gene Expression / drug effects*
  • Gonadotropin-Releasing Hormone / genetics
  • Gonadotropin-Releasing Hormone / metabolism
  • Goserelin / pharmacology*
  • Hippocampus / drug effects*
  • Male
  • Maze Learning / drug effects
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Orientation / drug effects*
  • RNA, Messenger / metabolism
  • Sex Characteristics
  • Sheep
  • Spatial Behavior / drug effects*
  • Time Factors


  • Antineoplastic Agents, Hormonal
  • Estrogen Receptor alpha
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Goserelin
  • Gonadotropin-Releasing Hormone