Abstract
Positive developmental impact of low stress-induced glucocorticoid levels in early development has been recognized for a long time, while possible involvement of mineralocorticoids in the stress response during the perinatal period has been neglected. The present study aimed at verifying the hypothesis that balance between stress-induced glucocorticoid and mineralocorticoid levels is changing during postnatal development. Hormone responses to two different stressors (insulin-induced hypoglycaemia and immune challenge induced by bacterial lipopolysaccharid) measured in 10-day-old rats were compared to those in adults. In pups corticosterone responses to both stressors were significantly lower than in adults, which corresponded well with the stress hyporesponsive period. Importantly, stress-induced elevations in aldosterone concentration were significantly higher in pups compared both to corticosterone elevations and to those in adulthood with comparable adrenocorticotropin concentrations in the two age groups. Greater importance of mineralocorticoids compared to glucocorticoids in postnatal period is further supported by changes in gene expression and protein levels of gluco- (GR) and mineralocorticoid receptors (MR) and selected enzymes measured by quantitative PCR and immunohystochemistry in the hypothalamus, hippocampus, prefrontal cortex, liver and kidney. Gene expression of 11beta-hydroxysteroid dehydrogenase 2 (11β-HSD2), an enzyme enabling preferential effects of aldosterone on mineralocorticoid receptors, was higher in 10-day-old pups compared to adult animals. On the contrary, the expression and protein levels of GR, MR and 11β-HSD1 were decreased. Presented results clearly show higher stress-induced release of aldosterone in pups compared to adults and strongly suggest greater importance of mineralocorticoids compared to glucocorticoids in stress during the postnatal period.
Highlights
Aldosterone is the main mineralocorticoid hormone involved in the control of water-electrolyte balance [1]
glucocorticoid receptor (GR) are activated when glucocorticoid concentrations are high as occurs during stress or at the peak of the circadian rhythm, while mineralocorticoid receptor (MR) are thought to be close to saturation at baseline, non-stress conditions and exhibit tonic influence on hypothalamo-pituitary-adrenocortical axis (HPA) output [6,7]
Present data provide the first evidence of increased aldosterone responses to stress stimuli during the postnatal period suggesting a shift in the balance between stress-induced glucocorticoid and mineralocorticoid hormone release during the development (Fig. 8)
Summary
Aldosterone is the main mineralocorticoid hormone involved in the control of water-electrolyte balance [1]. Aldosterone is released from the adrenal cortex in response to several stress stimuli [2]. Less attention has been given to aldosterone compared to cortisol and corticosterone (the main glucocorticoids in humans and rodents, respectively) mainly because they are acting on the same receptors and glucocorticoids are the dominant players. They have two types of receptors, namely the low affinity glucocorticoid receptor (GR) and the high affinity mineralocorticoid receptor (MR) [5]. GRs are activated when glucocorticoid concentrations are high as occurs during stress or at the peak of the circadian rhythm, while MRs are thought to be close to saturation at baseline, non-stress conditions and exhibit tonic influence on hypothalamo-pituitary-adrenocortical axis (HPA) output [6,7]
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