Tissue-specific Programming Expression of Glucocorticoid Receptors and 11β-HSDs by Maternal Perinatal Undernutrition in the HPA Axis of Adult Male Rats

Abstract

Maternal undernutrition leads to intrauterine growth retardation and predisposes to the development of pathologies in adulthood. The hypothalamo-pituitary-adrenal axis is a major target of early-life programming. We showed previously that perinatal maternal 50% food restriction leads to hypothalamo-pituitary-adrenal axis hyperactivity and disturbs glucocorticoid feedback in adult male rats. To try to better understand these alterations, we studied several factors involved in corticosterone sensitivity. We showed that unlike the restricted expression of 11β-HSD2 mRNA, the 11β-HSD1, glucocorticoid, and mineralocorticoid receptor genes are widely distributed in rat. In contrast to the hypothalamus, we confirmed that maternal undernutrition modulates hippocampal corticosterone receptor balance and leads to increased 11β-HSD1 gene expression. In the pituitary, rats exhibited a huge increase in both mRNA and mineralocorticoid receptor binding capacities as well as decreased 11β-HSD1/11β-HSD2 gene expression. Using in situ hybridization, we showed that the mineralocorticoid receptor gene was expressed in rat corticotroph cells and by other adenopituitary cells. In the adrenal gland, maternal food restriction decreased 11β-HSD2 mRNA. This study demonstrated that maternal food restriction has both long-term and tissue-specific effects on gene expression of factors involved in glucocorticoid sensitivity and that it could contribute, via glucocorticoid excess, to the development of adult diseases.

Key words

fetal programming - corticosterone - mineralocorticoid receptor - glucocorticoid receptor - 11β-HSD1 - 11β-HSD2 - perinatal food restriction

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1 These authors contributed equally to this work.

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