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Published on: March 12, 2019
Regulation of pituitary gene expression by adrenalectomy
Yuichiro Nishida1, Mayumi Yoshioka, Chester A Ray
1Department of Anatomy and Physiology, Functional Genomics Laboratory, Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, Laval University, Quebec City, Quebec, Canada.
Abstract:
Excessive secretion of adrenal hormones, such as glucocorticoid and mineralocorticoid, leads to metabolic syndrome, including insulin resistance, obesity, and hypertension. These metabolic abnormalities are ameliorated by adrenalectomy (ADX). To identify pituitary mediators for ADX-induced physiological alterations, such as weight loss and hypotension, we investigated the effect of ADX on the pituitary transcriptome using serial analysis of gene expression (SAGE). SAGE method is based on isolation of short sequence tags, which usually correspond to unique mRNA species. The SAGE libraries were constructed from pituitary gland of intact (n = 51) and ADX (n = 12) mice. Thirty-one transcripts were differentially expressed between intact and ADX. Three transcripts encoding for proopiomelanocortin and three other transcripts involved in regulation of hormone secretion (neuromedin B, proprotein convertase subtilisin/kexin type 2, and IA-2) were induced by ADX. In addition, ADX increased the expression levels of genes encoding for cation extracellular matrix (matrix gamma-carboxyglutamate protein) and transport (solute carrier family 22 member 17). Conversely, ADX downregulated two transcripts involved in mitochondrial oxidative phosphorylation (nicotinamide adenine dinucleotide (NADH) dehydrogenase 3 and cytochrome c oxidase 3). Moreover, ADX significantly modulated the expression levels of one gene with uncharacterized function and 20 novel transcripts. This study reveals alterations of pituitary gene expressions that may be associated with ADX-induced physiological changes including weight loss.
Insights
Adrenalectomy (ADX) in mice alters pituitary gene expression, potentially explaining weight loss and hypotension. This study used SAGE to identify key transcript changes following ADX.
Area of Science:
- Endocrinology
- Molecular Biology
- Genomics
Background:
- Excess adrenal hormone secretion causes metabolic syndrome (insulin resistance, obesity, hypertension).
- Adrenalectomy (ADX) ameliorates these metabolic abnormalities.
- Pituitary mediators of ADX-induced physiological changes like weight loss and hypotension are not fully understood.
Purpose of the Study:
- To identify pituitary gene expression changes in response to ADX.
- To investigate the role of the pituitary transcriptome in ADX-induced physiological alterations.
Main Methods:
- Serial Analysis of Gene Expression (SAGE) was employed to analyze pituitary transcriptomes.
- SAGE libraries were constructed from intact and ADX mice.
- Differential gene expression analysis was performed.
Main Results:
- Thirty-one transcripts showed differential expression between intact and ADX mice.
- ADX induced transcripts for proopiomelanocortin, neuromedin B, proprotein convertase subtilisin/kexin type 2, and IA-2.
- ADX altered expression of genes related to cation transport and mitochondrial oxidative phosphorylation, including nicotinamide adenine dinucleotide (NADH) dehydrogenase 3 and cytochrome c oxidase 3.
Conclusions:
- ADX induces significant alterations in pituitary gene expression.
- These transcriptomic changes may underlie ADX-associated physiological effects such as weight loss and hypotension.
- The study identified novel transcripts and genes with uncharacterized functions modulated by ADX.
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