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Gene array and real time PCR analysis of the adrenal sensitivity to adrenocorticotropic hormone in pig.

Hazard D, Liaubet L, Sancristobal M, Mormède P - BMC Genomics (2008)

Bottom Line: No change in the expression of known key regulator proteins of the ACTH signaling pathway or of steroidogenic enzymes was found.Higher TCA cycle activity in MS than in LW may thus result in higher steroidogenic activity and thus explain the typically higher cortisol levels in MS compared to LW.Moreover, up-regulation of Star and Ldlr genes in MS and/or in response to ACTH suggest that differences in the adrenal function between MS and LW may also involve mechanisms requisite for cholesterol supply to steroidogenesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratoire PsyNuGen, INRA UMR1286, CNRS UMR5226, Université de Bordeaux 2, 146 rue Léo-Saignat, F-33076 Bordeaux, France. dominique.hazard@bordeaux.inra.fr

ABSTRACT

Background: Variability in hypothalamic-pituitary-adrenal (HPA) axis activity has been shown to be influenced by genetic factors and related to great metabolic differences such as obesity. The aim of this study was to investigate molecular bases of genetic variability of the adrenal sensitivity to ACTH, a major source of variability, in Meishan (MS) and Large White (LW) pigs, MS being reported to exhibit higher basal cortisol levels, response to ACTH and fatness than LW. A pig cDNA microarray was used to identify changes in gene expression in basal conditions and in response to ACTH stimulation.

Results: Genotype and/or ACTH affected the expression of 211 genes related to transcription, cell growth/maintenance, signal transduction, cell structure/adhesion/extra cellular matrix and protein kinase/phosphatase activity. No change in the expression of known key regulator proteins of the ACTH signaling pathway or of steroidogenic enzymes was found. However, Mdh2, Sdha, Suclg2, genes involved in the tricarboxylic acid (TCA) pathway, were over-expressed in MS pigs. Higher TCA cycle activity in MS than in LW may thus result in higher steroidogenic activity and thus explain the typically higher cortisol levels in MS compared to LW. Moreover, up-regulation of Star and Ldlr genes in MS and/or in response to ACTH suggest that differences in the adrenal function between MS and LW may also involve mechanisms requisite for cholesterol supply to steroidogenesis.

Conclusion: The present study provides new potential candidate genes to explain genetic variations in the adrenal sensitivity to ACTH and better understand relationship between HPA axis activity and obesity.

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Related in: MedlinePlus

Cortisol concentrations (ng/ml plasma). Cortisol concentrations (ng/ml plasma) measured in Large White (LW) and Meishan (MS) piglets either untreated (control) or 1 hour after injection (ACTH) of a high dose (250 μg per animal) of 1–24 ACTH (Immediate synacthen). (n = 6 per experimental group, means ± SE).
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Figure 1: Cortisol concentrations (ng/ml plasma). Cortisol concentrations (ng/ml plasma) measured in Large White (LW) and Meishan (MS) piglets either untreated (control) or 1 hour after injection (ACTH) of a high dose (250 μg per animal) of 1–24 ACTH (Immediate synacthen). (n = 6 per experimental group, means ± SE).

Mentions: Comparison of plasma cortisol concentrations (figure 1) in control and ACTH-injected pigs showed significant breed (p < 0.0001) and treatment (p < 0.0001) effects and significant interaction (p ≤ 0.001). In control animals, basal cortisol levels were higher in Meishan pigs than in Large White pigs. Injection of ACTH increased cortisol levels in both genotypes but to a larger extent in Large White than in Meishan pigs.


Gene array and real time PCR analysis of the adrenal sensitivity to adrenocorticotropic hormone in pig.

Hazard D, Liaubet L, Sancristobal M, Mormède P - BMC Genomics (2008)

Cortisol concentrations (ng/ml plasma). Cortisol concentrations (ng/ml plasma) measured in Large White (LW) and Meishan (MS) piglets either untreated (control) or 1 hour after injection (ACTH) of a high dose (250 μg per animal) of 1–24 ACTH (Immediate synacthen). (n = 6 per experimental group, means ± SE).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2289818&req=5

Figure 1: Cortisol concentrations (ng/ml plasma). Cortisol concentrations (ng/ml plasma) measured in Large White (LW) and Meishan (MS) piglets either untreated (control) or 1 hour after injection (ACTH) of a high dose (250 μg per animal) of 1–24 ACTH (Immediate synacthen). (n = 6 per experimental group, means ± SE).
Mentions: Comparison of plasma cortisol concentrations (figure 1) in control and ACTH-injected pigs showed significant breed (p < 0.0001) and treatment (p < 0.0001) effects and significant interaction (p ≤ 0.001). In control animals, basal cortisol levels were higher in Meishan pigs than in Large White pigs. Injection of ACTH increased cortisol levels in both genotypes but to a larger extent in Large White than in Meishan pigs.

Bottom Line: No change in the expression of known key regulator proteins of the ACTH signaling pathway or of steroidogenic enzymes was found.Higher TCA cycle activity in MS than in LW may thus result in higher steroidogenic activity and thus explain the typically higher cortisol levels in MS compared to LW.Moreover, up-regulation of Star and Ldlr genes in MS and/or in response to ACTH suggest that differences in the adrenal function between MS and LW may also involve mechanisms requisite for cholesterol supply to steroidogenesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratoire PsyNuGen, INRA UMR1286, CNRS UMR5226, Université de Bordeaux 2, 146 rue Léo-Saignat, F-33076 Bordeaux, France. dominique.hazard@bordeaux.inra.fr

ABSTRACT

Background: Variability in hypothalamic-pituitary-adrenal (HPA) axis activity has been shown to be influenced by genetic factors and related to great metabolic differences such as obesity. The aim of this study was to investigate molecular bases of genetic variability of the adrenal sensitivity to ACTH, a major source of variability, in Meishan (MS) and Large White (LW) pigs, MS being reported to exhibit higher basal cortisol levels, response to ACTH and fatness than LW. A pig cDNA microarray was used to identify changes in gene expression in basal conditions and in response to ACTH stimulation.

Results: Genotype and/or ACTH affected the expression of 211 genes related to transcription, cell growth/maintenance, signal transduction, cell structure/adhesion/extra cellular matrix and protein kinase/phosphatase activity. No change in the expression of known key regulator proteins of the ACTH signaling pathway or of steroidogenic enzymes was found. However, Mdh2, Sdha, Suclg2, genes involved in the tricarboxylic acid (TCA) pathway, were over-expressed in MS pigs. Higher TCA cycle activity in MS than in LW may thus result in higher steroidogenic activity and thus explain the typically higher cortisol levels in MS compared to LW. Moreover, up-regulation of Star and Ldlr genes in MS and/or in response to ACTH suggest that differences in the adrenal function between MS and LW may also involve mechanisms requisite for cholesterol supply to steroidogenesis.

Conclusion: The present study provides new potential candidate genes to explain genetic variations in the adrenal sensitivity to ACTH and better understand relationship between HPA axis activity and obesity.

Show MeSH
Related in: MedlinePlus