Insulin-like growth factor (IGF) 2 plays a fundamental role in prenatal growth and development. The IGF2 gene is imprinted, with the paternally inherited copy being active and the maternal copy being silenced in most tissues. During development, the expression of IGF2 is sexually dimorphic in some tissues and this is thought to be involved in the development of some sexually dimorphic features. For example, IGF2 expression is reported to be higher in the male brain compared to females, but less is known regarding specific brain areas and cell types. As the hypothalamus is implicitly implicated in the control of sexually dimorphic endocrine functions and glial cells participate in this control, we asked whether their expression of IGF2 and other members of the IGF system is sexually dimorphic. Our aims were to: 1) Determine if the overall expression of IGF2 is sexually dimorphic in specific brain regions, including the hypothalamus, and 2) Compare the expression of the IGF system in hypothalamic astrocytes from male and female neonatal rats. For tissue analysis, cerebellum, hypothalamus and frontal cortex were dissected from 2-day old Wistar males and females. Primary hypothalamic astrocyte cultures were prepared from 2-day old male and female Wistar rats and grown under standard conditions for 10 days. Total RNA was extracted, and RT-PCR performed. There were no differences between the sexes in expression of IGF1 or IGF2 in cerebellum or hypothalamus. In frontal cortex, IGF1 expression was higher in females (P<0.05) compared to males. In contrast, in hypothalamic astrocyte cultures IGF1 expression was higher in males (P<0.01) and IGF2 mRNA levels higher in females (P<0.05). None of the remaining IGF family members analyzed (pregnancy-associated plasma protein-A, IGF-binding proteins 2, 3, 4 and 5 and stanniocalcin-2) were different between the sexes at this age. In conclusion, although overall IGF1 and IGF2 expression was not sexually dimorphic in the hypothalamus at post-natal day 2, the expression of these growth factors by hypothalamic astrocytes differed between neonatal males and females. Thus, these glial cells could participate in the development of sexually dimorphic neuroendocrine systems. It remains to be determined if this sex difference in IGF expression by astrocytes is age and anatomically specific.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology