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
References
1 These authors contributed equally to this work.
Correspondence
Didier.Vieau@univ-lille1.fr
