Repeated maternal dexamethasone treatments in late gestation increases 11β-hydroxysteroid dehydrogenase type 1 expression in the hippocampus of the newborn rat

Wan, Shunlun; Hao, Rusong; Sun, Kang

doi:10.1016/j.neulet.2005.02.066

Cited by 17 publications

(8 citation statements)

References 33 publications

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“…Confirming this, a relationship between social stress and visceral fat 11betaHSD1 expression has been found in male mice (Kuo et al, 2007). Moreover, an increase of 11betaHSD1 enzymatic activity has been described in liver and omental adipose tissue as well as in hippocampus of rats prenatally exposed to different stressogenic conditions (Nammi et al, 2007;Wan et al, 2005).…”

Section: Stress Hpa Axis Dysregulation and Obesitymentioning

confidence: 55%

Chronic social stress, hedonism and vulnerability to obesity: Lessons from Rodents

Coccurello¹,

D’Amato²,

Moles³

2009

Neuroscience & Biobehavioral Reviews

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Section: Stress Hpa Axis Dysregulation and Obesitymentioning

confidence: 55%

Chronic social stress, hedonism and vulnerability to obesity: Lessons from Rodents

Coccurello¹,

D’Amato²,

Moles³

2009

Neuroscience & Biobehavioral Reviews

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“…The detection of increased 11␤-HSD-1 reductase activity in an already chronically elevated CORT environment has been documented elsewhere (38). Furthermore, a recent study showed that DEX exposure during the last week of gestation significantly increases hippocampal 11␤-HSD-1 mRNA and protein expression in newborn rat offspring compared with controls (54). Because DEX administration to pregnant dams results in a precipitous decrease in maternal levels of serum CORT (10,36), the adult offspring in our study were effectively exposed to a unique in utero environment of low maternal CORT and 11␤-HSD-1; C) mRNA expression in hippocampal tissues from control and DEX-exposed rats under both unrestrained and restraint-stressed conditions as determined by real-time PCR analysis.…”

Section: Discussionmentioning

confidence: 81%

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

Shoener¹,

Baig²,

Page³

2006

American Journal of Physiology-Regulatory, Integrative and Comp

101

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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-␤-hydroxysteroid dehydrogenase-1 (11␤-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 11␤-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 11␤-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. mineralcorticoid receptor:glucocorticoid receptor balance; 11-␤-hydroxysteroid dehydrogenase-1; circadian rhythm; restraint stress A CONSIDERABLE BODY OF EVIDENCE indicates that the limbic system is a central modulator of hypothalamic-pituitary-adrenal (HPA) axis activity (18,41) and that it is exquisitely sensitive to fluctuations in circulating corticosteroids (27,28,56). Corticosteroid receptors, which include both mineralcorticoid receptors (MR) and glucocorticoid receptors (GR), are highly expressed in this system (29,44) and are colocalized in distinct regions, particularly the hippocampus (51, 53). In contrast, nonlimbic sites, such as the prefrontal cortex, hypothalamus, and pituitary, express predominantly GR (10, 43).

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“…Similarly, neonatal lambs born to nutrient-restricted ewes had elevated 11␤-HSD1 mRNA expression in perirenal adipose tissue (66). In the rat fetus, maternal dexamethasone treatment increased 11␤-HSD1 expression in the lungs (27) and the hippocampus (64). In addition, overfeeding of postnatal rats upregulated 11␤-HSD1 mRNAs in mesenteric adipose tissue (10).…”

Section: Discussionmentioning

confidence: 95%

Increased 11β-hydroxysteroid dehydrogenase type-1 and hexose-6-phosphate dehydrogenase in liver and adipose tissue of rat offspring exposed to alcohol in utero

Nammi¹,

Dembele²,

Nyomba³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Nammi S, Dembele K, Nyomba BL. Increased 11␤-hydroxysteroid dehydrogenase type-1 and hexose-6-phosphate dehydrogenase in liver and adipose tissue of rat offspring exposed to alcohol in utero. Am J Physiol Regul Integr Comp Physiol 292: R1101-R1109, 2007. First published November 22, 2006 doi:10.1152/ajpregu.00255.2006.-Rat offspring prenatally exposed to alcohol display features of metabolic syndrome characterized by a low birth weight, catch-up growth, dyslipidemia, and insulin-resistant diabetes with increased gluconeogenesis, during adult life. Gluconeogenesis is partly regulated by cyclic AMP-and glucocorticoid-dependent mechanisms. Glucocorticoid action at the receptor level depends on its circulating concentrations and is amplified at the prereceptor level by 11␤-hydroxysteroid dehydrogenase type 1 (11␤-HSD1), which regenerates active glucocorticoids from inactive forms. To determine whether 11␤-HSD1 is dysregulated in this rat model, we examined the expression and enzyme activity of 11␤-HSD1 and its regulator enzyme hexose-6-phosphate dehydrogenase (H6PD) in the liver of postnatal day 7 (neonatal) and 3-mo-old (adult) rat offspring prenatally exposed to alcohol. Measurements of 11␤-HSD1 and H6PD were also performed in the omental fat of adult rat offspring. In both neonatal and adult rats, prenatal alcohol exposure resulted in increased tissue corticosterone concentrations, increased expression, and oxoreductase activity of 11␤-HSD1, and a parallel increase of H6PD expression. The data suggest that due to both transcriptional and posttranscriptional dysregulations, rats exposed to alcohol early in life have increased 11␤-HSD1 activity, which may explain insulin-resistant diabetes in these animals later in life. prenatal exposure; programming SEVERAL PRENATAL ADVERSE FACTORS have been implicated in the pathogenesis of chronic diseases in adulthood. The importance of these factors was first recognized by epidemiological studies describing associations between intrauterine growth restriction (IUGR) and insulin resistance, type 2 diabetes, and cardiovascular diseases later in life (6). Since the offspring exposed to such prenatal factors were small at birth, these abnormalities are considered to be a consequence of IUGR. In animal models of IUGR employing malnutrition (44), placental ischemia (53), glucocorticoid exposure (8), or diabetes (62) during pregnancy, the offspring develop insulin resistance, glucose intolerance, and obesity with aging.

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Repeated maternal dexamethasone treatments in late gestation increases 11β-hydroxysteroid dehydrogenase type 1 expression in the hippocampus of the newborn rat

Cited by 17 publications

References 33 publications

Chronic social stress, hedonism and vulnerability to obesity: Lessons from Rodents

Chronic social stress, hedonism and vulnerability to obesity: Lessons from Rodents

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

Increased 11β-hydroxysteroid dehydrogenase type-1 and hexose-6-phosphate dehydrogenase in liver and adipose tissue of rat offspring exposed to alcohol in utero

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