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

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, corticotropin-releasing hormone and 11β-hydroxysteroid dehydrogenase type 1 (11β-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 11β-HSD1 was increased by vitamin A deficiency in the hypothalamus (+62.5%) as in the hippocampus (+104.7%), which could lead to a higher production of corticosterone locally and contribute to alteration of the hippocampus. RA supplementation treatment restored corticosterone concentrations and 11β-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 11β-HSD1-mediated deleterious action on cognitive performances during ageing.

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Prenatal exposure to dexamethasone alters hippocampal drive on hypothalamic-pituitary-adrenal axis activity in adult male rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00757.2004 ◽

2006 ◽

Vol 290 (5) ◽

pp. R1366-R1373 ◽

Cited By ~ 72

Author(s):

Jennifer A. Shoener ◽

Romana Baig ◽

Kathleen C. Page

Keyword(s):

Hpa Axis ◽

Adult Male ◽

Restraint Stress ◽

Exposed Group ◽

Late Gestation ◽

Male Rats ◽

Mrna Levels ◽

Hypothalamic Pituitary Adrenal ◽

Hpa Axis Activity ◽

Circulating Levels

Glucocorticoids are essential for normal hypothalamic-pituitary-adrenal (HPA) axis activity; however, recent studies warn that exposure to excess endogenous or synthetic glucocorticoid during a specific period of prenatal development adversely affects HPA axis stability. We administered dexamethasone (DEX) to pregnant rats during the last week of gestation and investigated subsequent HPA axis regulation in adult male offspring in unrestrained and restraint-stressed conditions. With the use of real-time PCR and RIA, we examined the expression of regulatory genes in the hippocampus, hypothalamus, and pituitary, including corticotropin-releasing hormone (CRH), arginine vasopressin (AVP), glucocorticoid receptors (GR), mineralcorticoid receptors (MR), and 11-β-hydroxysteroid dehydrogenase-1 (11β-HSD-1), as well as the main HPA axis hormones, adrenal corticotropic hormone (ACTH) and corticosterone (CORT). Our results demonstrate that the DEX-exposed group exhibited an overall change in the pattern of gene expression and hormone levels in the unrestrained animals. These changes included an upregulation of CRH in the hypothalamus, a downregulation of MR with a concomitant upregulation of 11β-HSD-1 in the hippocampus, and an increase in circulating levels of both ACTH and CORT relative to unrestrained control animals. Interestingly, both DEX-exposed and control rats exhibited an increase in pituitary GR mRNA levels following a 1-h recovery from restraint stress; however, the increased expression in DEX-exposed rats was significantly less and was associated with a slower return to baseline CORT compared with controls. In addition, circulating levels of ACTH and CORT as well as hypothalamic CRH and hippocampal 11β-HSD-1 expression levels were significantly higher in the DEX-exposed group compared with controls following restraint stress. Taken together, these data demonstrate that late-gestation DEX exposure in rats is associated with persistent changes in both the modulation of HPA axis activity and the HPA axis-mediated response to stress.

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Neonatal monosodium glutamate treatment alters both the activity and the sensitivity of the rat hypothalamo-pituitary-adrenocortical axis

Journal of Endocrinology ◽

10.1677/joe.0.1410497 ◽

1994 ◽

Vol 141 (3) ◽

pp. 497-503 ◽

Cited By ~ 23

Author(s):

P J Larsen ◽

J D Mikkelsen ◽

D Jessop ◽

S L Lightman ◽

H S Chowdrey

Keyword(s):

Hpa Axis ◽

Restraint Stress ◽

Acute Stress ◽

Monosodium Glutamate ◽

Plasma Corticosterone ◽

Mrna Levels ◽

Plasma Acth ◽

Corticotrophin Releasing Factor ◽

Acute And Chronic Stress ◽

Corticosterone Response

Abstract We have investigated the effects of monosodium glutamate (MSG) lesioning of the arcuate nucleus on both central and peripheral components of the hypothalamo-pituitary-adrenocortical (HPA) axis under basal conditions and under acute and chronic stress. Plasma ACTH levels were lower in MSG-lesioned rats (27 ± 7 pg/ml) compared with controls (71 ± 18 pg/ml) while corticosterone levels were elevated (523 ± 84 ng/ml compared with 176 ± 34 ng/ml). Quantititative in situ hybridization histochemistry revealed that corticotrophin-releasing factor mRNA levels in the medial parvocellular part of the hypothalamic paraventricular nucleus were significantly lower in MSG-treated rats. MSG lesioning resulted in an enhanced response of corticosterone to restraint stress (1309 ± 92 ng/ml compared with 628 ± 125 ng/ml in sham-lesioned animals), while ACTH responses to restraint stress in MSG-lesioned and sham-MSG groups were not significantly different (160 ± 24 pg/ml and 167 ± 24 pg/ml respectively). These data suggest that MSG-lesioned rats have an increased adrenocortical sensitivity. In rats subjected to the chronic osmotic stimulus of drinking 2% saline for 12 days, plasma ACTH levels were significantly reduced (15 ± 5 pg/ml) and the ACTH and corticosterone responses to restraint stress were eliminated. ACTH levels were also reduced in MSG-treated animals given 2% saline and the ACTH response to acute stress remained absent in these animals. However, a robust corticosterone response to restraint stress was observed in saline-treated MSG-lesioned rats. These data demonstrate that MSG lesioning results in elevated basal and stress-induced plasma corticosterone, and restores the adrenocortical response to stress which is absent in chronically osmotically stimulated rats. The evidence is consistent with the suggestion that MSG lesions a pathway involved in tonic inhibition of the HPA axis. In addition, the adrenocortical sensitivity to ACTH and other secretagogues may be increased in MSG-treated animals. Journal of Endocrinology (1994) 141, 497–503

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Intrahypothalamic Estradiol Modulates Hypothalamus-Pituitary-Adrenal-Axis Activity in Female Rats

Endocrinology ◽

10.1210/en.2011-2176 ◽

2012 ◽

Vol 153 (7) ◽

pp. 3337-3344 ◽

Cited By ~ 27

Author(s):

J. Liu ◽

P. H. Bisschop ◽

L. Eggels ◽

E. Foppen ◽

E. Fliers ◽

...

Keyword(s):

Hpa Axis ◽

Restraint Stress ◽

Acute Stress ◽

Plasma Corticosterone ◽

Female Rats ◽

Ovariectomized Rats ◽

Stress Exposure ◽

Ici 182,780 ◽

Hpa Axis Activity

Estrogen plays an important role in the regulation of the hypothalamus-pituitary-adrenal (HPA)-axis, but the neuroendocrine pathways and the role of estrogen receptor (ER) subtypes involved in specific aspects of this interaction remain unknown. In a first set of experiments, we administered estradiol (E2) intravenously, intracerebroventricularly, and by intrahypothalamic microdialysis to ovariectomized rats to measure plasma corticosterone (CORT) concentrations from carotid artery blood. Systemic infusion of E2 did not increase plasma CORT, but intracerebroventricular E2 induced a 3-fold CORT increase (P = 0.012). Local E2 infusions in the hypothalamic paraventricular nucleus (PVN) significantly increased plasma CORT (P < 0.001). A similar CORT increase was seen after PVN infusion of the ERα agonist propylpyrazoletriol, whereas the ERβ agonist diarylpropiolnitrile had no effect. In a second set of experiments, we investigated whether E2 modulates the HPA-axis response to acute stress by administering E2 agonists or its antagonist ICI 182,780 into the PVN during restraint stress exposure. After 30 min of stress exposure, plasma CORT had increased 5.0-fold (P < 0.001). E2 and propylpyrazoletriol administration in the PVN enhanced the stress-induced plasma CORT increase (8-fold vs. baseline), whereas ICI 182,780 and diarylpropiolnitrile reduced it, as compared with both E2 and vehicle administration in the PVN. In conclusion, central E2 modulates HPA-axis activity both in the basal state and during restraint stress. In the basal condition, the stimulation is mediated by ERα-sensitive neurons, whereas during stress, it is mediated by both ERα and ERβ.

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Research Recommendations for Applying Vitamin A-Labelled Isotope Dilution Techniques to Improve Human Vitamin A Nutrition

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000185 ◽

2014 ◽

Vol 84 (Supplement 1) ◽

pp. 52-59 ◽

Cited By ~ 5

Author(s):

Sherry A. Tanumihardjo ◽

Anura V. Kurpad ◽

Janet R. Hunt

Keyword(s):

Public Health ◽

Vitamin A ◽

Vitamin A Deficiency ◽

Human Subjects ◽

The Body ◽

Pool Size ◽

Serum Retinol ◽

Vitamin A Status ◽

Status Assessment ◽

Total Body

The current use of serum retinol concentrations as a measurement of subclinical vitamin A deficiency is unsatisfactory for many reasons. The best technique available for vitamin A status assessment in humans is the measurement of total body pool size. Pool size is measured by the administration of retinol labelled with stable isotopes of carbon or hydrogen that are safe for human subjects, with subsequent measurement of the dilution of the labelled retinol within the body pool. However, the isotope techniques are time-consuming, technically challenging, and relatively expensive. There is also a need to assess different types of tracers and doses, and to establish clear guidelines for the use and interpretation of this method in different populations. Field-friendly improvements are desirable to encourage the application of this technique in developing countries where the need is greatest for monitoring the risk of vitamin A deficiency, the effectiveness of public health interventions, and the potential of hypervitaminosis due to combined supplement and fortification programs. These techniques should be applied to validate other less technical methods of assessing vitamin A deficiency. Another area of public health relevance for this technique is to understand the bioconversion of β-carotene to vitamin A, and its relation to existing vitamin A status, for future dietary diversification programs.

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Effects of alprazolam on cholecystokinin-tetrapeptide (CCK-4) induced panic and hypothalamic-pituitary-adrenal (HPA) axis activity

Pharmacopsychiatry ◽

10.1055/s-2003-825321 ◽

2004 ◽

Vol 36 (05) ◽

Author(s):

D Eser ◽

P Zwanzger ◽

S Aicher ◽

C Schüle ◽

TC Baghai ◽

...

Keyword(s):

Hpa Axis ◽

Hypothalamic Pituitary Adrenal ◽

Hpa Axis Activity

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Genotype Effects on β-Carotene Conversion to Vitamin A: Implications on Reducing Vitamin A Deficiency in the Philippines

Food and Nutrition Bulletin ◽

10.1177/03795721211060229 ◽

2021 ◽

pp. 037957212110602

Author(s):

Mark Pretzel P. Zumaraga ◽

Jose Maria Reynaldo Apollo Arquiza ◽

Mae Anne Concepcion ◽

Leah Perlas ◽

Ma. Neda Alcudia-Catalma ◽

...

Keyword(s):

Vitamin A ◽

Children And Adolescents ◽

Vitamin A Deficiency ◽

The Philippines ◽

Fisher Exact Test ◽

National Capital Region ◽

Nutrition Survey ◽

Vitamin A Status ◽

Genotype Frequencies

Background: The study aimed to identify two beta-carotene 15,15′-monooxygenase (BCMO1) mutations, namely R267S and A379V, and determine their association with vitamin A status among Filipinos 6 to 19 years old respondents of the 2013 Philippine National Nutrition Survey living in the National Capital Region. Materials and Methods: This study followed cross-sectional design. Whole blood specimen was collected in the morning and was used as source of genomic DNA and serum for retinol concentration determination. Fisher exact test was performed to determine whether genotype frequencies were associated to retinol concentrations/vitamin A deficiency status. A level of P < .05 was identified as significant. Results: A total of 693 Filipino children and adolescents were included. Of the 693, there were at least 7.6% who bears the combined mutations for R267S + A379V. Association analysis showed that an inverse relationship exists between the A379V TT variant and vitamin A status. Although the exact role of these identified polymorphisms on retinol/carotenoid metabolism need to be confirmed in dedicated functional studies. Conclusion: This study has identified for the first time the presence of 2 nonsynonymous genetic variants/mutations in the coding region of BCMO1 gene. Interestingly, one of these two variants, the A379V T, was found to be associated with vitamin A status. It is, therefore, warranted to investigate the role of BCMO1 variants for the success of supplementation programs and fortification efforts among vulnerable populations in this region. Genetic variability should be considered for future provitamin A supplementation recommendations among children and adolescents in the Philippines.

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Vitamin A Supplementation and Child Morbidity and Mortality in Developing Countries

Food and Nutrition Bulletin ◽

10.1177/156482659401500414 ◽

1994 ◽

Vol 15 (4) ◽

pp. 1-9 ◽

Cited By ~ 27

Author(s):

George H. Beaton ◽

Reynaldo Martorell ◽

Kristan A. Aronson ◽

Barry Edmonston ◽

George McCabe. A. Catharine Ross ◽

...

Keyword(s):

Vitamin A ◽

Respiratory Infections ◽

Vitamin A Deficiency ◽

Meta Analysis ◽

Clinical Signs ◽

Vitamin A Status ◽

Child Morbidity ◽

Age Profile ◽

Mortality Trials ◽

Low Prevalence

A meta-analysis of eight mortality trials indicates that improving the vitamin A status of children aged six months to five years reduced mortality rates by about 23% in populations with at least low prevalence of clinical signs of vitamin A deficiency. The observed effect of supplementation, described in terms of relative risk (RR), was RR =0.77 (95% confidence interval 0.68–0.88; p < .001) and did not differ by sex or age. However, the number of lives saved was greater at younger ages because of higher mortality. A significant RR was shown for deaths attributed to diarrhoea and measles, but not for respiratory infection. Variability among the trials in effects was apparent, but attempts to explain it by descriptors of the population (baseline anthropometric status, prevalence of xerophthalmia, age profile, baseline mortality) were unsuccessful. Owing to the lack of data, firm conclusions could not be reached about effectiveness in children of less than six months and in settings where biochemical but not clinical evidence of vitamin A deficiency exists. Information about morbidity outcomes from about two dozen studies was reviewed. No consistent effects on frequency or prevalence of diarrhoeal and respiratory infections were found. Improvement in vitamin A status did appear to reduce severe morbidity, particularly in children with measles.

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Cassava with enhanced β-carotene maintains adequate vitamin A status in Mongolian gerbils (Meriones unguiculatus) despite substantial cis-isomer content

British Journal Of Nutrition ◽

10.1017/s0007114508184720 ◽

2009 ◽

Vol 102 (3) ◽

pp. 342-349 ◽

Cited By ~ 25

Author(s):

Julie A. Howe ◽

Bussie Maziya-Dixon ◽

Sherry A. Tanumihardjo

Keyword(s):

Vitamin A ◽

Vitamin A Deficiency ◽

Meriones Unguiculatus ◽

Provitamin A ◽

Carotenoid Content ◽

Mongolian Gerbils ◽

Serum Retinol ◽

Vitamin A Status ◽

Isomer Content ◽

Β Carotene

Efforts to increase β-carotene in cassava have been successful, but the ability of high-β-carotene cassava to prevent vitamin A deficiency has not been determined. Two studies investigated the bioefficacy of provitamin A in cassava and compared the effects of carotenoid content and variety on vitamin A status in vitamin A-depleted Mongolian gerbils (Meriones unguiculatus). Gerbils were fed a vitamin A-free diet 4 weeks prior to treatment. In Expt 1, treatments (ten gerbils per group) included 45 % high-β-carotene cassava, β-carotene and vitamin A supplements (intake matched to high-β-carotene cassava group), and oil control. In Expt 2, gerbils were fed cassava feeds with 1·8 or 4·3 nmol provitamin A/g prepared with two varieties. Gerbils were killed after 4 weeks. For Expt 1, liver vitamin A was higher (P < 0·05) in the vitamin A (1·45 (sd 0·23) μmol/liver), lower in the control (0·43 (sd 0·10) μmol/liver), but did not differ from the β-carotene group (0·77 (sd 0·12) μmol/liver) when compared with the high-β-carotene cassava group (0·69 (sd 0·20) μmol/liver). The bioconversion factor was 3·7 μg β-carotene to 1 μg retinol (2 mol:1 mol), despite 48 % cis-β-carotene [(Z)-β-carotene] composition in cassava. In Expt 2, cassava feed with 4·3 nmol provitamin A/g maintained vitamin A status. No effect of cassava variety was observed. Serum retinol concentrations did not differ. β-Carotene was detected in livers of gerbils receiving cassava and supplements, but the cis-to-trans ratio in liver differed from intake. Biofortified cassava adequately maintained vitamin A status and was as efficacious as β-carotene supplementation in the gerbil model.

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Vitamin A Status and Hepatic Drug Metabolism in the Rat

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y73-002 ◽

1973 ◽

Vol 51 (1) ◽

pp. 6-11 ◽

Cited By ~ 51

Author(s):

G. C. Becking

Keyword(s):

Vitamin A ◽

Drug Metabolism ◽

Vitamin A Deficiency ◽

Hepatic Drug Metabolism ◽

Deficient Diet ◽

Hepatic Drug ◽

Vitamin A Status ◽

Cytochrome P 450 ◽

Liver Vitamin

The effect of vitamin A status on hepatic drug metabolism was studied in rats. Animals were fed diets with and without vitamin A for 20 and 25 days. Weight gains of control and deficient animals were not significantly different, whereas liver vitamin A levels had decreased to less than 10% of control animals after 20 days and were essentially zero after eating the deficient diet for 25 days. Aniline metabolism in vitro and aminopyrine metabolism in vitro and in vivo were significantly lower in male weanling rats fed a vitamin A deficient diet for 20 days. No alteration in in vitro p-nitrobenzoic acid metabolism was noted after 25 days on the test. Vitamin A deficiency did not alter microsomal protein levels or cytochrome c reductase activity but deficient animals did have a lower microsomal cytochrome P-450 content. Hepatic enzyme activities and cytochrome P-450 levels were restored to values approaching those found in control animals by feeding vitamin A deficient rats the vitamin A containing diet for 21 days. Liver vitamin A levels were markedly increased after re-feeding studies but were still significantly lower than control animals.

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