Vitamin A regulates hypothalamic–pituitary–adrenal axis status in LOU/C rats

Abstract

The aim of this study was to explore the involvement of retinoids in the hypoactivity and hyporeactivity to stress of the hypothalamic-pituitary-adrenal (HPA) axis in LOU/C rats. We measured the effects of vitamin A deficiency administered or not with retinoic acid (RA) on plasma corticosterone in standard conditions and in response to restraint stress and on hypothalamic and hippocampal expression of corticosteroid receptors, corticotropinreleasing hormone and 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) in LOU/C rats. Interestingly, under control conditions, we measured a higher plasma concentration of retinol in LOU/C than in Wistar rats, which could contribute to the lower basal activity of the HPA axis in LOU/C rats. Vitamin A deficiency induced an increased HPA axis activity in LOU/C rats, normalized by RA administration. Compared with LOU/C control rats, vitamin A-deficient rats showed a delayed and heightened corticosterone response to restraint stress. The expression of corticosteroid receptors was strongly decreased by vitamin A deficiency in the hippocampus, which could contribute to a less efficient feedback by corticosterone on HPA axis tone. The expression of 11b-HSD1 was increased by vitamin A deficiency in the hypothalamus (C62.5%) as in the hippocampus (C104.7%), which could lead to a higher production of corticosterone locally and contribute to alteration of the hippocampus. RA supplementation treatment restored corticosterone concentrations and 11b-HSD1 expression to control levels. The high vitamin A status of LOU/C rats could contribute to their low HPA axis activity/reactivity and to a protective effect against 11b-HSD1-mediated deleterious action on cognitive performances during ageing.

Cortisol levels in beluga whales (Delphinapterus leucas): Setting a benchmark for Marine Protected Area monitoring

“…However, pre-treatment with vitamin E in pigs reduced peak cortisol levels after stress challenge (Webel et al 1998). Similarly, vitamin A (retinol and retinoic acid) has been found to antagonize the HPA-axis and cortisol production, and vice versa (Enwonwu and Phillips 2004;Marissal-Arvy et al 2013), suggesting a possible mechanistic link between these vitamins and cortisol. This antagonism may be the result of interactions of active vitamin A compounds on glucocorticoid receptors and expression of dehydrogenase enzymes important for glucocorticoid activation (Anstead 1998;Marissal-Arvy et al 2013).…”

“…Similarly, vitamin A (retinol and retinoic acid) has been found to antagonize the HPA-axis and cortisol production, and vice versa (Enwonwu and Phillips 2004;Marissal-Arvy et al 2013), suggesting a possible mechanistic link between these vitamins and cortisol. This antagonism may be the result of interactions of active vitamin A compounds on glucocorticoid receptors and expression of dehydrogenase enzymes important for glucocorticoid activation (Anstead 1998;Marissal-Arvy et al 2013). Further exploration of the opposing relationships between vitamins A/E and cortisol are needed to define direct interactions from cross correlation with common predictors.…”

Vitamin A status regulates glucocorticoid availability in Wistar rats: consequences on cognitive functions and hippocampal neurogenesis?

“…Both the hyperactivity of hippocampal 11β-HSD1 and elevated plasma CORT, are correlated with impairments in hippocampal-dependent memory tasks during aging (Yau et al, 2001; Holmes et al, 2010; Yau and Seckl, 2012). Interestingly, the inhibitory effects of RA and vitamin A supplementation have been shown on the expression and the activity of 11β-HSD1, in differentiated C2C12 myotubes (Aubry and Odermatt, 2009), in obese rat liver (Sakamuri et al, 2011) but also in vitamin A-deficient LOU/C rats (Arvy et al, 2013). Indeed, in this latter study, the VAD-induced up-regulation of the hippocampal expression of 11β-HSD1 has been associated to an increased Hypothalamic-Pituitary-Adrenal (HPA) axis activity in basal and stress conditions which has been normalized by a RA treatment (Arvy et al, 2013).…”

“…Interestingly, the inhibitory effects of RA and vitamin A supplementation have been shown on the expression and the activity of 11β-HSD1, in differentiated C2C12 myotubes (Aubry and Odermatt, 2009), in obese rat liver (Sakamuri et al, 2011) but also in vitamin A-deficient LOU/C rats (Arvy et al, 2013). Indeed, in this latter study, the VAD-induced up-regulation of the hippocampal expression of 11β-HSD1 has been associated to an increased Hypothalamic-Pituitary-Adrenal (HPA) axis activity in basal and stress conditions which has been normalized by a RA treatment (Arvy et al, 2013). Finally, a RA treatment inhibits the hypersecretion of CORT in an experimental model of the Cushing's syndrome (Paez-Pereda et al, 2001) suggesting that it could be used as a successful treatment to reverse endocrine and cognitive alterations found in stress-related disorders.…”

Diabetes and Insulin Injection Modalities: Effects on Hepatic and Hippocampal Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 in Juvenile Diabetic Male Rats

“…(12), using a highly specific antibody provided by H. Vaudry (University of Rouen, France). Briefly, after steroid extraction of plasma samples with absolute ethanol, total corticosterone was measured by competition between cold corticosterone and 3 H-corticosterone for the specific anti-corticosterone antibody.…”