Perinatal Malnutrition Programs Sympathoadrenal and Hypothalamic‐Pituitary‐Adrenal Axis Responsiveness to Restraint Stress in Adult Male Rats

Abstract

In humans, an altered control of cortisol secretion was reported in adult men born with a low birth weight making the hypothalamic-pituitary-adrenal (HPA) axis a possible primary target of early life programming. In rats, we have recently shown that maternal food restriction during late pregnancy induces both an intrauterine growth retardation and an overexposure of fetuses to maternal corticosterone, which disturb the development of the HPA axis in offspring. The first aim of this work was to investigate, in adult male rats, whether perinatal malnutrition has long-lasting effects on the HPA axis activity during both basal and stressful conditions. Moreover, as the HPA axis and sympathetic nervous system are both activated by stress, the second aim of this work was to investigate, in these rats, the adrenomedullary catecholaminergic system under basal and stressful conditions. This study was conducted on 4-month-old male rats malnourished during their perinatal life and on age-matched control animals. Under basal conditions, perinatal malnutrition reduced body weight and plasma corticosteroid-binding globulin (CBG) level but increased mineralocorticoid receptor (MR) gene expression in CA1 hippocampal area. After 30 min of restraint, perinatally malnourished (PM) rats showed increased plasma noradrenaline, adrenocorticotropin hormone (ACTH) and corticosterone concentrations similarly as controls, but calculated plasma-free corticosterone concentration was significantly higher and adrenaline level lower than controls. During the phase of recovery, PM rats showed a rapid return of plasma ACTH and corticosterone concentrations to baseline levels in comparison with controls. These data suggest that in PM rats, an elevation of basal concentrations of corticosterone, in face of reduced CBG and probably increased hippocampal MR lead to a much larger impact of corticosterone on target cells that mediate the negative-feedback mechanism on the activities of both the HPA axis and sympathoadrenal one.

Effects of dehydration on endocrine regulation of the electrolyte and fluid balance and atrial natriuretic peptide-binding sites in perinatally malnourished adult male rats

“…This confirms previous data in rats obtained in our laboratory, in which body weight was studied at weaning (40) or at 4 months of age (52). Thus, limited nutritional intake during the last week of gestation and lactation leads to persistent failure to catch up in body weight in the adult rat offspring, despite nutritional rehabilitation for several months.…”

Prenatal Programming of Hypertension

“…Increased plasma noradrenaline level in response to stress has been described in rat offspring at 4 mo of age after perinatal malnutrition (90), suggesting dysfunction of the sympathetic system. Altered fetal sympathetic activity, assessed by the response in heart rate to BP variation, has been reported in rats and sheep (42,43,56,57), and the suggestion has been made that low BP during prenatal life may result in resetting of baroreflex control and thereby contribute to the later development of hypertension (42).…”

Maternal Undernutrition Programs Offspring Adrenal Expression of Steroidogenic Enzymes

“…4,5 Most of these studies have focused primarily on characterization of the adult offspring hypothalamic-pituitary axis and changes in expression of GC/MC receptors in the central nervous system. 4,[6][7][8] The effect of maternal undernutrition on expression of adrenal GC/MC receptors remains elusive. Glucocorticoids play an essential role in the stress response and have been proposed to alter signal transduction in the adrenal cortex thereby regulating adrenocorticotropic hormone (ACTH) sensitivity.…”