Maternal Perinatal Undernutrition Alters Neuronal and Neuroendocrine Differentiation in the Rat Adrenal Medulla at Weaning

Molendi-Coste, Olivier; Grumolato, Luca; Laborie, Christine; Lésage, Jean; Maubert, Eric; Ghzili, Hafida; Vaudry, Hubert; Anouar, Youssef; Breton, Christophe; Vieau, Didier

doi:10.1210/en.2005-1331

Cited by 21 publications

(31 citation statements)

References 44 publications

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“…Undernutrition during gestation and lactation induces changes in the development of adrenal chromaffin cells, resulting in increased catecholamine levels at weaning (34,35). We have also observed that maternal protein restriction only during lactation programs for high catecholamine synthesis and secretion at adulthood (22).…”

Section: E946supporting

confidence: 53%

Programming of rat adrenal medulla by neonatal hyperleptinemia: adrenal morphology, catecholamine secretion, and leptin signaling pathway

Trevenzoli¹,

Pinheiro²,

Conceição³

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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Trevenzoli IH, Pinheiro CR, Conceição EP, Oliveira E, Passos MC, Lisboa PC, Moura EG. Programming of rat adrenal medulla by neonatal hyperleptinemia: adrenal morphology, catecholamine secretion, and leptin signaling pathway. Am J Physiol Endocrinol Metab 298: E941-E949, 2010. First published February 9, 2010 doi:10.1152/ajpendo.00734.2009.-Leptin serum concentration in early life is an important factor for adequate future development of the offspring. Previously, we demonstrated that hyperleptinemia on lactation programmed for hyperleptinemia, central leptin resistance with lower expression of the long form of leptin receptor at hypothalamus, and higher medullary catecholamine levels with cardiovascular consequences at adulthood. The central objective of this study was to determine the direct effect of leptin on adrenal medullary function of adult rats that were leptin treated during lactation. Adrenal morphology was also accessed. Recombinant murine leptin was injected in the pups during the first 10 days of life (group L, leptin-programmed) or at adulthood during 6 days (group LC). The controls of both experiments received saline (groups C and CC). Both treatments resulted in hyperleptinemia at 150 days old (ϩ78% and 2-fold increase, respectively; P Ͻ 0.05). Programmed animals showed hypertrophy of adrenal and higher adrenal catecholamine content at 150 days old (3-fold increase, P Ͻ 0.05), and no changes were observed in the LC group. However, LC rats had lower adrenal content of tyrosine hydroxylase (Ϫ17%, P Ͻ 0.05). Leptin-programmed rats had a lower response to leptin in vitro stimulation (Ϫ22%, P Ͻ 0.05) and lower expression of key proteins of the leptin signaling pathway, leptin receptor and janus tyrosine kinase 2 in the medullas (Ϫ61% and Ϫ29%, respectively, P Ͻ 0.05). However, they presented higher expression of phosphorylated signal transducer and activator of transcription 3 (ϩ2-fold, P Ͻ 0.05). Leptin treatment at adulthood did not affect these parameters. The higher catecholamine synthesis and secretion in the leptin-programmed rats observed in our previous study does not seem to be a consequence of the direct effect of leptin on the medullas. We suggest that the hyperleptinemia of the programmed animals increases adrenal medullary function through sympathetic nervous system activation. In conclusion, high leptin levels on lactation program the activity of the sympathoadrenal system at adulthood that may contribute to the development of adult chronic diseases such as hypertension.

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Section: E946supporting

confidence: 53%

Programming of rat adrenal medulla by neonatal hyperleptinemia: adrenal morphology, catecholamine secretion, and leptin signaling pathway

Trevenzoli¹,

Pinheiro²,

Conceição³

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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“…Additionally, neural regulation of PNMT is mediated by splanchnic nerve innervation as part of the SA system (Kvetň anský & Pacák 1995). It is suggested that the SA system can also be programmed for development of hypertension, with subsequent effects within the adrenal medulla, such as enhanced activity of chromaffin cells as early as 1 week of age (Molendi-Coste et al 2006). Thus, increased activity of adrenal chromaffin cells may be dependent on dysregulation of either one or both the HPA and SA axes.…”

Section: Discussionmentioning

confidence: 99%

Prenatal glucocorticoid exposure programs adrenal PNMT expression and adult hypertension

Nguyen¹,

Khurana

Peltsch

et al. 2015

Journal of Endocrinology

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Prenatal exposure to glucocorticoids (GCs) programs for hypertension later in life. The aim of the current study was to examine the impact of prenatal GC exposure on the postnatal regulation of the gene encoding for phenylethanolamine N-methyltransferase (PNMT), the enzyme involved in the biosynthesis of the catecholamine, epinephrine. PNMT has been linked to hypertension and is elevated in animal models of hypertension. Male offspring of Wistar-Kyoto dams treated with dexamethasone (DEX) developed elevated systolic, diastolic and mean arterial blood pressure compared to saline-treated controls. Plasma epinephrine levels were also elevated in adult rats exposed to DEX in utero. RT-PCR analysis revealed adrenal PNMT mRNA was higher in DEX exposed adult rats. This was associated with increased mRNA levels of transcriptional regulators of the PNMT gene: Egr-1, AP-2, and GR. Western blot analyses showed increased expression of PNMT protein, along with increased Egr-1 and GR in adult rats exposed to DEX in utero. Furthermore, gel mobility shift assays showed increased binding of Egr-1 and GR to DNA. These results suggest that increased PNMT gene expression via altered transcriptional activity is a possible mechanism by which prenatal exposure to elevated levels of GCs may program for hypertension later in life.

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“…Catecholamine content of the plasma was determined as previously described in detail using high-performance liquid chromatography coupled with electrochemical detection after alumina extraction (29). Plasma glucagon content was determined with a commercial available enzyme-linked immunosorbent assay (ELISA) kit (Glucagon Quantikine; R&D Systems).…”

Section: Plasma Assaysmentioning

confidence: 99%

Hypothalamic Apelin/Reactive Oxygen Species Signaling Controls Hepatic Glucose Metabolism in the Onset of Diabetes

Drougard

Duparc

Brénachot

et al. 2014

Antioxidants & Redox Signaling

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Aims: We have previously demonstrated that central apelin is implicated in the control of peripheral glycemia, and its action depends on nutritional (fast versus fed) and physiological (normal versus diabetic) states. An intracerebroventricular (icv) injection of a high dose of apelin, similar to that observed in obese/diabetic mice, increase fasted glycemia, suggesting (i) that apelin contributes to the establishment of a diabetic state, and (ii) the existence of a hypothalamic to liver axis. Using pharmacological, genetic, and nutritional approaches, we aim at unraveling this system of regulation by identifying the hypothalamic molecular actors that trigger the apelin effect on liver glucose metabolism and glycemia. Results: We show that icv apelin injection stimulates liver glycogenolysis and gluconeogenesis via an over-activation of the sympathetic nervous system (SNS), leading to fasted hyperglycemia. The effect of central apelin on liver function is dependent of an increased production of hypothalamic reactive oxygen species (ROS). These data are strengthened by experiments using lentiviral vectormediated over-expression of apelin in hypothalamus of mice that present over-activation of SNS associated to an increase in hepatic glucose production. Finally, we report that mice fed a high-fat diet present major alterations of hypothalamic apelin/ROS signaling, leading to activation of glycogenolysis. Innovation/Conclusion: These data bring compelling evidence that hypothalamic apelin is one master switch that participates in the onset of diabetes by directly acting on liver function. Our data support the idea that hypothalamic apelin is a new potential therapeutic target to treat diabetes. Antioxid. Redox Signal. 20, 557-573.

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Maternal Perinatal Undernutrition Alters Neuronal and Neuroendocrine Differentiation in the Rat Adrenal Medulla at Weaning

Cited by 21 publications

References 44 publications

Programming of rat adrenal medulla by neonatal hyperleptinemia: adrenal morphology, catecholamine secretion, and leptin signaling pathway

Programming of rat adrenal medulla by neonatal hyperleptinemia: adrenal morphology, catecholamine secretion, and leptin signaling pathway

Prenatal glucocorticoid exposure programs adrenal PNMT expression and adult hypertension

Hypothalamic Apelin/Reactive Oxygen Species Signaling Controls Hepatic Glucose Metabolism in the Onset of Diabetes

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