Fetal undernutrition induces overexpression of CRH mRNA and CRH protein in hypothalamus and increases CRH and corticosterone in plasma during postnatal life in the rat

Núñez, Harold; Ruíz, Samuel; Soto-Moyano, Rubén; Navarrete, Mario; Valladares, Luis; White, Allan; Pérez, Hernán

doi:10.1016/j.neulet.2008.10.014

Cited by 32 publications

(16 citation statements)

References 34 publications

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“…This result supports the idea of an impaired afferent catecholaminergic pathway to the PVN in the overweight early-overfed group, because CRF is upregulated by NA (Cole & Sawchenko 2002). Interestingly, fetally fetal undernourished adult rats present high proCRF expression (Nú ñez et al 2008), as well as enhanced brain noradrenergic synthesis and release (Soto--Moyano et al 1998a,b).…”

Section: Discussionsupporting

confidence: 64%

Pro-TRH and pro-CRF expression in paraventricular nucleus of small litter-reared fasted adult rats

Aréchiga-Ceballos

Alvarez-Salas

Matamoros-Trejo

et al. 2014

Journal of Endocrinology

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Neuroendocrine axes adapt to nutrient availability. During fasting, the function of the hypothalamus–pituitary–thyroid axis (HPT) is reduced, whereas that of the hypothalamus–pituitary–adrenal axis (HPA) is increased. Overfeeding-induced hyperleptinemia during lactation may alter the regulatory set point of neuroendocrine axes and their adaptability to fasting in adulthood. Hyperleptinemia is developed in rodents by litter size reduction during lactation; adult rats from small litters become overweight, but their paraventricular nucleus (PVN) TRH synthesis is unchanged. It is unclear whether peptide expression still responds to nutrient availability. PVN corticotropin-releasing factor (CRF) expression has not been evaluated in this model. We analyzed adaptability of HPT and HPA axes to fasting-induced low leptin levels of reduced-litter adult rats. Offspring litters were reduced to 2–3/dam (early-overfed) or maintained at 8/dam (controls, C). At 10 weeks old, a subset of animals from each group was fasted for 48 h and leptin, corticosterone, and thyroid hormones serum levels were analyzed. In brain, expressions of leptin receptor, NPY and SOCS3, were evaluated in arcuate nucleus, and those of proTRH and proCRF in PVN by real-time PCR. ProTRH expression in anterior and medial PVN subcompartments was assayed byin situhybridization. Early-overfed adults developed hyperphagia and excessive weight, together with decreased proTRH expression in anterior PVN, supporting the anorexigenic effects of TRH. Early-overfed rats presented low PVN proTRH synthesis, whereas fasting did not induce a further reduction. Fasting-induced stress was unable to increase corticosterone levels, contributing to reduced body weight loss in early-overfed rats. We concluded that early overfeeding impaired the adaptability of HPT and HPA axes to excess weight and fasting in adults.

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Section: Discussionsupporting

confidence: 64%

Pro-TRH and pro-CRF expression in paraventricular nucleus of small litter-reared fasted adult rats

Aréchiga-Ceballos

Alvarez-Salas

Matamoros-Trejo

et al. 2014

Journal of Endocrinology

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“…Nunez et al [31] obtained similar basal CRH plasma levels in 40-day-old Wistar rat pups (29.1 ± 4.2 pg/ml) in plasma after acidification and C18 column extraction using the same RIA kit. In earlier studies, low basal plasma levels of CRH ranging from 5 to 13 pg/ml were detected in rats [20,32,33] as monitored using CRH antibodies, tracers and RIA conditions developed within investigators’ laboratories, leading to detection limits of approximately 5 pg/ml [20,23,33].…”

Section: Discussionmentioning

confidence: 81%

“…It is to note that the CRH antibody was raised against the full-length synthetic 41-aa CRH peptide that is conserved in humans and rats and recognizes full-length 41-aa CRH (technical note of the company). Nonetheless, it cannot be excluded that the CRH immunoreactivity measured in the plasma by us and others [31,38] with this CRH antibody originates from CRH precursor or degraded and/or processed pro-CRH to form endogenously circulating different CRH molecular forms, as it has been characterized for other circulating peptides such as cholecystokinin and peptide YY [39,40]. Existing evidence indicates that the major form of CRH detected in human placenta under conditions of adequate protease inhibition is the unprocessed pro-CRH, unlike the mature CRH [41].…”

Section: Discussionmentioning

confidence: 88%

Lipopolysaccharide Increases Plasma Levels of Corticotropin-Releasing Hormone in Rats

Goebel¹,

Stengel²,

Wang³

et al. 2010

Neuroendocrinology

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Background: Corticotropin-releasing hormone (CRH) is expressed in the brain, immune cells and the gut, where gene expression is upregulated by lipopolysaccharide (LPS) 6 h after injection. Whether these changes are reflected by increased circulating levels of CRH and adrenocorticotropic hormone (ACTH) is unknown. Methods: LPS (100 µg/kg) was injected intraperitoneally in conscious rats, and blood processed for CRH using the new RAPID (reduced temperatures, acidification, protease inhibition, isotopic exogenous controls and dilution) method compared with EDTA blood with or without plasma methanol extraction. Hormone levels were measured by commercial radioimmunoassay. Results: The RAPID method improved blood recovery of ¹²⁵I-CRH in vitro compared to EDTA only added to the blood without or with methanol extraction (90.8 ± 2.0 vs. 66.9 ± 2.6 and 47.5 ± 2.0%, respectively; p < 0.001 vs. RAPID). Basal CRH levels from blood processed by the RAPID method were 28.9 ± 2.8 pg/ml, and by other methods below the radioimmunoassay detection limit (<10 pg/ml). At 6 h after LPS, CRH plasma levels increased significantly by 2.9 times, and in the proximal colon tended to decrease (–27.6 ± 5.7%; p > 0.05), while circulating levels were unchanged at 3 or 4 h. ACTH levels rose compared to control rats (135.3 ± 13.8 vs. 101.4 ± 6.0 pg/ml; p < 0.05) 30 min after the increase in CRH, while at 3 or 6 h after LPS, the levels were not changed. Conclusion: Intraperitoneal LPS induces a delayed rise in plasma CRH levels associated with an elevation in ACTH plasma levels 30 min later, suggesting that under conditions of immune challenge, CRH of peripheral origin may also contribute to pituitary activation, as detected using the RAPID method of blood processing, which improves CRH recovery.

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“…Elevated levels of circulating maternal catecholamines cause vasoconstriction of placental blood vessels, reducing placental blood supply and hence impairing the delivery of oxygen and nutrients to the foetuses. Given that hypoxia and nutrient restriction activate the foetal HPA axis (Edwards & McMillen 2002, Roelfsema et al 2005) and elicit foetal sympathetic-adrenomedullary stress responses (Gu & Jones 1986), these responses may contribute to the foetal programming of HPA axis responsivity and anxiety-like behaviour in the adult offspring , Lingas & Matthews 2001, Nunez et al 2008, Fan et al 2009, Wang et al 2013. The adrenal medulla also secretes b-endorphin following stress exposure, which may cross the placenta to influence the development of the foetal brain (Sandman et al 1997).…”

Section: Role For Catecholamines?mentioning

confidence: 99%

Effects of maternal exposure to social stress during pregnancy: consequences for mother and offspring

2013

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A suboptimal in utero environment, for example, as a result of maternal stress, can have detrimental effects on the pregnancy and long-term adverse 'programming' effects on the offspring. This article focuses on the effects of prenatal social stress on the mother, her pregnancy and the offspring, since these issues have ethological relevance in both animals and humans. The consequences of social stress exposure depend on when during pregnancy the stress occurs, and many of the effects on the offspring are sex specific. Social stress during early pregnancy tends to result in pregnancy loss, whereas stress exposure later in pregnancy, when the mother has already invested considerable resources in the foetuses, results in programmed offspring of low birth weight: a risk factor for various adulthood diseases. Neuroendocrine and behavioural responses to stress in the offspring are particularly sensitive to foetal programming by prenatal stress, indicated by enhanced hypothalamo-pituitary-adrenal (HPA) axis responses and increased anxiety behaviour, which result from permanent changes in the offspring's brain. The dysregulation of HPA axis function may also interfere with other systems, for example, the hypothalamic-pituitary-gonadal axis, as there is evidence for alterations in steroidogenesis, reproductive potential and impaired reproductive/social behaviours in prenatally stressed offspring. Prenatal social stress also programmes future maternal behaviour, highlighting the potential for negative phenotypes to be transmitted to future generations. The possible mechanisms through which maternal stress during pregnancy is transmitted to the foetuses and the foetal brain is programmed by prenatal stress and the potential to overwrite programming of the offspring are discussed.Reproduction (2013) 146 R175-R189

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Fetal undernutrition induces overexpression of CRH mRNA and CRH protein in hypothalamus and increases CRH and corticosterone in plasma during postnatal life in the rat

Cited by 32 publications

References 34 publications

Pro-TRH and pro-CRF expression in paraventricular nucleus of small litter-reared fasted adult rats

Pro-TRH and pro-CRF expression in paraventricular nucleus of small litter-reared fasted adult rats

Lipopolysaccharide Increases Plasma Levels of Corticotropin-Releasing Hormone in Rats

Effects of maternal exposure to social stress during pregnancy: consequences for mother and offspring

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