Sex differences and left–right asymmetries in expression of insulin and insulin-like growth factor-1 receptors in developing rat hippocampus

Abstract

Sex differences and laterality of rat hippocampus with respect to insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (InsR) expression as two important contributors to/regulators of developmental and cognitive functions were examined using real-time PCR and western blot analysis at P0, P7 and P14. Expression of the IGF-1R gene was lowest at P0 in all studied hippocampi. In males, we found the highest expression at P7 in the right hippocampus, and at P14 in the left one. In contrast, the peaked IGF-1R expression occurred at P7 in female hippocampi independent of laterality. Hippocampal InsR expression in males decreased significantly between P0 and P7, followed by a marked upregulation at P14. Conversely, the expression of InsR in females peaked at P7 and then decreased again significantly at P14. We found significant interhemispheric differences in IGF-1R mRNA levels in both male and female hippocampi at different time points. In contrast, we only found significant interhemispheric differences in InsR mRNA expression in P14 male rats, with higher values in the left hippocampus. Interestingly, changes in mRNA expression and in protein levels followed the same developmental pattern, indicating that IGF-1R and InsR transcription is not subject to modulatory effects during the first two weeks of development. These findings indicate that there are prominent interhemispheric and sex differences in IGF-1R and InsR expression in the developing rat hippocampus, suggesting a probable mechanism for the control of gender and laterality differences in development and function of the hippocampus.

Estrogen-IGF-1 interactions in neuroprotection: Ischemic stroke as a case study

“…All males subject to this protocol developed mesial temporal lobe epilepsy when measured 3-4 months of age, while none of the females showed epilepsy (Desgent et al, 2012). While IGF-1 and IGFR expression was not reported in this study, peak IGFR expression in the hippocampus occurs earlier in females than males (Hami et al, 2012), indicating the availability of an early protective substrate in females. Similarly, sex differences are also evident in seizure behavior following ethanol withdrawal.…”

“…Interestingly, laterality differences were seen in males and females but at different time points. These time course changes suggest that gender and laterality differences in IGF-1 may influence function and development of the hippocampus (Hami et al, 2012). …”

Oestradiol synthesized by female neurons generates sex differences in neuritogenesis

“…Whether oestradiol is activating a different set of ERs in male and female neurons to promote Ngn3 expression and neuritogenesis merits future investigation. On the other hand, ER signalling interacts with the signalling of the receptors for other factors, such as insulin like growth factor-I, Wnt or Notch25, whose expression and activity may differ in male and female neurons262728.…”

Modeling Fetal Alcohol Spectrum Disorder: Validating an Ex Vivo Primary Hippocampal Cell Culture System

“…It has been proposed that re-methylation of the DMR within the Igf2 gene is primarily regulated by the embryo's sex chromosomes. Sex differences in the expression of hippocampal Insr has been found as being higher in male than in female rats on postnatal day one (Hami et al, 2012), but no sex differences in fetal Insr expression has been reported to date prior to the prenatal testosterone surge.…”