Sexual Dimorphism in Expression of Insulin and Insulin-like Growth Factor-I Receptors in Developing Rat Cerebellum

The insulin and insulin-like growth factor-1 (IGF-1) are considered to play important roles in brain development; and their cognate receptors -InsR and IGF-1R- localized within distinct brain regions including cerebellum. Using Real-Time PCR and western blot analysis, we compared the expression of InsR and IGF-1R in male and female developing rat cerebellum at P0, P7, and P14. At all time points studied, the cerebellar expression of IGF-1R, both at mRNA and protein levels was higher than that of InsR. The lowest InsR and IGF-1R mRNA and protein levels were measured in the neonate cerebellum, independent of gender. In males, the highest InsR and IGF-1R mRNA and protein expression were found at P7. InsR and IGF-1R expression increased significantly between P0 and P7, followed by a marked downregulation at P14. In contrast, in females, mRNA and protein levels of InsR and IGF-1R remain unchanged between P0 and P7, and are upregulated at P14. Therefore, peaked InsR and IGF-1R expression in female cerebelli occurred at P14. Interestingly, changes in mRNA expression and in protein levels followed the same developmental pattern, indicating that InsR and IGF-1R transcription is not subject to modulatory effects during the first 2 weeks of development. These findings indicate that there are prominent sexual differences in InsR and IGF-1R expression in the developing rat cerebellum, suggesting a probable mechanism for the control of gender differences in development and function of the cerebellum.