Gene array analysis of the effects of chronic adrenocorticotropic hormone in vivo on immature rat adrenal glands

Lee, Julie J.; Widmaier, Eric P.

doi:10.1016/j.jsbmb.2005.01.026

Cited by 13 publications

(17 citation statements)

References 51 publications

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“…Note: an increase in the ⌬ Ct value represents a decrease in mRNA expression. changes were not observed with pharmacological doses of ACTH in neonatal rat pups (16). Therefore, the effects described next appear to be primarily mediated by hypoxia.…”

Section: Discussionmentioning

confidence: 78%

“…Total RNA from pooled adrenal glands (n ϭ 4 pooled samples per Normoxia or Hypoxia) was isolated with TRIzol reagent (Invitrogen Life Technologies, Carlsbad, CA) and column purified (Qiagen, Valencia, CA) as described previously (16). RNA quality was assessed spectrophotometrically on the basis of the A260/A280 ratio.…”

Section: Methodsmentioning

confidence: 99%

“…Changes in adrenal gene expression due to hypoxia were measured by microarray analysis, as described previously (16). In brief, double-stranded DNA was synthesized from 10 g of total RNA using a Superscript cDNA Synthesis Kit (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

“…Evaluation of data from microarray analysis was performed as described in detail previously (16). In brief, scanned images were quantified by GeneChip Operating Software 1.1 (Affymetrix).…”

Section: Methodsmentioning

confidence: 99%

“…Fold-change in expression was calculated from the average signal intensity of each group. A modified version of the false-discovery rate (FDR) method was used to assess significance of results (16). To identify genes significantly affected by hypoxia, genes with an FDR Յ0.25 and a minimum fold-change of Ϯ1.3 were selected.…”

Section: Methodsmentioning

confidence: 99%

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Microarray and real-time PCR analysis of adrenal gland gene expression in the 7-day-old rat: effects of hypoxia from birth

Bruder

Lee

Widmaier

et al. 2007

Physiological Genomics

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Bruder ED, Lee JJ, Widmaier EP, Raff H. Microarray and real-time PCR analysis of adrenal gland gene expression in the 7-day-old rat: effects of hypoxia from birth. Physiol Genomics 29: 193-200, 2007. First published January 9, 2007; doi:10.1152/physiolgenomics.00245.2006.-We hypothesize that changes in adrenal gene expression mediate the increased plasma corticosterone and steroidogenesis in rat pups exposed to hypoxia from birth. In the current study, rat pups (with their dams) were exposed to hypoxia from birth and compared with pups from normoxic dams fed ad libitum or pair fed to match the decreased maternal food intake that occurs during hypoxia. Microarray analysis was performed, followed by verification with real-time PCR. Furthermore, the expression of selected genes involved in adrenal function was analyzed by real-time PCR, regardless of microarray results. Hypoxia increased plasma ACTH and corticosterone, while food restriction had no effect. Microarray revealed that many of the genes affected by hypoxia encode proteins that require molecular oxygen (monooxygenases, oxidoreductases, and electron transport), whereas only a few genes known to be involved in adrenal steroidogenesis were affected. Interestingly, the expression of genes involved in mitochondrial function and intermediary metabolism was increased by hypoxia. Real-time PCR detected a small but significant increase in the expression of Cyp21a1 mRNA in the hypoxic adrenal. When decreased maternal food intake was controlled for, the effects of hypoxia were more pronounced, in that real-time PCR detected significant increases in the expression of Star (244%), Cyp21a1 (208%), and Ldlr (233%). The present study revealed that increased plasma corticosterone in rat pups was due to hypoxia per se, and not as a result of decreased food intake by the hypoxic dam. Furthermore, hypoxia induced changes in gene expression that account for more productive and efficient steroidogenesis. steroidogenesis; neonatal; mRNA; adrenal cortex; corticosterone; ACTH SYSTEMIC HYPOXIA IS A CONDITION frequently encountered in the neonatal intensive care unit, is often a complication of preterm birth, and is associated with significant morbidity and mortality (9, 19). The ability to survive a hypoxic episode depends on coordinated physiological responses by a number of systems. These responses include, but are not limited to, adaptations in metabolic, hemodynamic, digestive, and cardiorespiratory function (8,10,13,17,22). A coordinated endocrine response is also a critical component (23,26). The ability of the neonatal hypothalamic-pituitary-adrenal (HPA) axis to mount a response to low oxygen is of paramount importance. A majority of preterm infants lack the capacity for an adrenocortical response to exogenous ACTH and physiological stressors, and this leads to enhanced inflammation and decreased pulmonary function requiring ventilation (15, 35).In the neonatal rat, there is a unique developmental aspect to the maturation of the adrenocortical response to stressors such a...

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Section: Discussionmentioning

confidence: 78%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Evaluation of data from microarray analysis was performed as described in detail previously (16). In brief, scanned images were quantified by GeneChip Operating Software 1.1 (Affymetrix).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Microarray and real-time PCR analysis of adrenal gland gene expression in the 7-day-old rat: effects of hypoxia from birth

Bruder

Lee

Widmaier

et al. 2007

Physiological Genomics

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Fetal and NeonatalHPAAxis

Wood

Walker

2015

Comprehensive Physiology

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Stress is an integral part of life. Activation of the hypothalamus-pituitary-adrenal (HPA) axis in the adult can be viewed as mostly adaptive to restore homeostasis in the short term. When stress occurs during development, and specifically during periods of vulnerability in maturing systems, it can significantly reprogram function, leading to pathologies in the adult. Thus, it is critical to understand how the HPA axis is regulated during developmental periods and what are the factors contributing to shape its activity and reactivity to environmental stressors. The HPA axis is not a passive system. It can actively participate in critical physiological regulation, inducing parturition in the sheep for instance or being a center stage actor in the preparation of the fetus to aerobic life (lung maturation). It is also a major player in orchestrating mental function, metabolic, and cardiovascular function often reprogrammed by stressors even prior to conception through epigenetic modifications of gametes. In this review, we review the ontogeny of the HPA axis with an emphasis on two species that have been widely studied-sheep and rodents-because they each share many similar regulatory mechanism applicable to our understanding of the human HPA axis. The studies discussed in this review should ultimately inform us about windows of susceptibility in the developing brain and the crucial importance of early preconception, prenatal, and postnatal interventions designed to improve parental competence and offspring outcome. Only through informed studies will our public health system be able to curb the expansion of many stress-related or stress-induced pathologies and forge a better future for upcoming generations.

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Transcriptome Analysis of Adrenocortical Cells in Health and Disease

Ishii

2014

Cellular Endocrinology in Health and Disease

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Gene array analysis of the effects of chronic adrenocorticotropic hormone in vivo on immature rat adrenal glands

Cited by 13 publications

References 51 publications

Microarray and real-time PCR analysis of adrenal gland gene expression in the 7-day-old rat: effects of hypoxia from birth

Microarray and real-time PCR analysis of adrenal gland gene expression in the 7-day-old rat: effects of hypoxia from birth

Fetal and NeonatalHPAAxis

Transcriptome Analysis of Adrenocortical Cells in Health and Disease

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