Comparison of Stress-Induced Changes in Adults and Pups: Is Aldosterone the Main Adrenocortical Stress Hormone during the Perinatal Period in Rats?

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.

View on Aldosterone and the Brain Revisited

“…In adult rats, the response was quite opposite; the increase in stress-induced aldosterone concentrations was only mild, whereas the elevation of corticosterone was much more pronounced. The physiological significance of increased aldosterone secretion during stress in the early postnatal period is supported by our findings of altered expression of mineralocorticoid and glucocorticoid receptors in the hypothalamus, hippocampus, and prefrontal cortex and in particular by increased expression of 11β-HSD2 [56].…”

“…In a joint project with the Institute of Experimental Medicine, Hungarian Academy of Sciences, we have demonstrated that 10-day rat pups showed increased rather than reduced response of aldosterone to several acute stress stimuli. Stressinduced rise in aldosterone concentrations was significantly higher in pups compared to that in adulthood as well as compared to the rise in corticosterone [56]. In adult rats, the response was quite opposite; the increase in stress-induced aldosterone concentrations was only mild, whereas the elevation of corticosterone was much more pronounced.…”

Aldosterone Signals the Onset of Depressive Behaviour in a Female Rat Model of Depression along with SSRI Treatment Resistance

“…Interestingly, a shift from corticosterone to aldosterone also occurs early in life. Recently, a greater importance of mineralocorticoids compared to glucocorticoids in stress during the postnatal period has been suggested based on the observation of a higher stress-induced release of aldosterone in rat pups compared to adults [38]. …”

Epigenetic Programming of Synthesis, Release, and/or Receptor Expression of Common Mediators Participating in the Risk/Resilience for Comorbid Stress-Related Disorders and Coronary Artery Disease

“…Changes in circadian rhythms, including that of the HHA axis, have been associated with the development of metabolic syndrome and its CV consequences [ 61 ]. Although the mechanisms involved in the regulation of this axis remain unknown, there is participation of the density of glucocorticoid and mineralocorticoid receptors in different target regions of the brain such as the hypothalamus or the hippocampus [ 62 ]. Changes in the activity of the HHA axis might also be due to variations in the hormone concentrations or to the density of peripheral receptors [ 63 ].…”