The aim of this study was to determine the influence of maternal
undernutrition (MUN) on maternal and offspring adrenal steroidogenic
enzymes. Pregnant Sprague-Dawley rats were 50% food-restricted from day 10 of gestation until delivery. Control animals received ad libitum food. Offspring were killed on day 1 of life (P1) and at 9 months. We determined the
messenger RNA (
mRNA) expression of steroidogenic
enzymes by real-time
reverse transcriptase polymerized chain reaction (RT-PCR). Maternal
undernutrition inhibited maternal adrenal expression of P450
cholesterol side-chain cleavage enzyme (
CYP11A1),
11 beta-hydroxylase (
CYP11B1),
aldosterone synthase (
CYP11B2), and
adrenocorticotropic hormone (
ACTH) receptor (
ACTH-R; MC2 gene) compared with control offspring. There was a marked downregulation in the expression of
CYP11B1,
CYP11B2, 11 β-
hydroxysteroid dehydrogenase type 1 and 2 (HSD1 and HSD2),
CYP11A1,
ACTH receptor,
steroidogenic acute regulatory protein (STAR), and
mineralocorticoid receptor (MCR; NR3C2 gene)
mRNA in P1 MUN offspring (both genders), with no changes in
glucocorticoid receptor (GCR). Quantitative immunohistochemical analysis confirmed the PCR data for GCR and MCR in P1 offspring and demonstrated lower expression of
leptin receptor protein (Ob-Ra/Ob-Rb) and
mRNA in P1 MUN offspring. In 9-month adult male MUN offspring, the expression of HSD1,
CYP11A1,
CYP11B2, Ob-Ra/Ob-Rb, and GCR
mRNA were significantly upregulated with a trend toward an increase in
ACTH-R and a decrease in
17 alpha-hydroxylase (CYP17A1) expression. In adult female MUN offspring, similar to males, the expression of
CYP11A1,
ACTH-R, and Ob-Rb
mRNA were increased, whereas GCR and CYP17A1
mRNA were decreased. These results indicate that the adrenal gland is a target of nutritional programming. In utero
undernutrition has a global suppressive effect on maternal and P1 offspring adrenal steroidogenic
enzymes in association with reduced circulating
corticosterone levels in P1 offspring, which may be secondary to a negative feedback from elevated maternal GC levels and or
leptin levels in MUN dams. Gender-specific differences in steroidogenic
enzyme expression were found in adult MUN offspring. The common finding of increased
ACTH receptor expression in MUN adults of both genders suggests an increased sensitivity of these offspring to stress.