Domestication Effects on Stress Induced Steroid Secretion and Adrenal Gene Expression in Chickens

Fallahsharoudi, Amir; Kock, Neil de; Johnsson, Martin; Ubhayasekera, Sarojini J.K.A.; Bergquist, Jonas; Wright, Dominic; Jensen, Per

doi:10.1038/srep15345

Cited by 56 publications

(53 citation statements)

References 82 publications

(106 reference statements)

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“…Overall, these results are in line with the previous observations that WL display a lower poststress peak in corticosterone plasma concentrations (Ericsson et al, 2014;Fallahsharoudi et al, 2015). However, we must be somewhat careful with inferring biological effects based on measurement of gene expression.…”

Section: Effects Of Domestication On Stress-related Gene Expressionsupporting

confidence: 90%

“…Many of these traits are consistent with the domestic phenotype. For example, domesticated chickens have a higher growth rate, become sexually mature earlier, show lower fearfulness and display an attenuated hormonal stress response compared to the RJF (Campler et al, 2009;Ericsson et al, 2014;Fallahsharoudi et al, 2015;Kerje et al, 2003;Schütz et al, 2004).…”

Section: Chicken Domesticationmentioning

confidence: 99%

“…Studies have shown that the chickens of the domesticated breed White Leghorn demonstrate an attenuated peak compared with Red Junglefowl (Ericsson et al, 2014;Fallahsharoudi et al, 2015).…”

Section: Domestication and The Stress Responsementioning

confidence: 99%

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Domestication and early experiences in chickens: Behavior, stress and gene expression

Løtvedt¹

2017

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A number of animal species have undergone domestication, the process of becoming adapted to living in captivity and in proximity to humans. Common for these species is that they have all developed certain traits, including changes to coat color, body size and level of fearfulness. This has been termed the domestic phenotype. Among these traits is also an attenuation of the response to stress, both behaviorally and physiologically. Thus, release of glucocorticoids such as cortisol or corticosterone is lower in domesticated species. However, the underlying mechanism for this is not yet well understood. In this thesis, we have investigated genetic mechanisms for the attenuation of the physiological stress response in ancestral chickens, the Red Junglefowl, and domesticated chickens, the White Leghorn.We found a number of genes that differed in expression between the two breeds in several tissues involved in the stress response. Among the most interesting findings were lower expression of genes involved in production and secretion of ACTH in the pituitary, and in the production of glucocorticoids in the adrenal glands, in the domesticated White Leghorns. We also found higher expression of the glucocorticoid receptor in White Leghorns, indicating that they may have a more efficient negative feedback of the physiological stress response.We then investigated the transcriptome of the chicken pituitary more closely, and we discovered that a number of genes highly involved in several important physiological axes showed differential expression between the ancestral and the domesticated breed. Among these were genes involved in the stress response, the reproductive system, and in metabolism and growth. As these traits are modified in domesticated species, our results suggest that changes to gene expression in the pituitary may be an important underlying factor of the domestic phenotype.A separate aim of this thesis was to investigate effects of hatching time in chickens on their subsequent phenotype. Time of hatching constitutes an early experience that may differ between individuals, and we therefore hypothesized that differences in hatching time would affect chickens later in life. While a number of studies have been performed on hatching time and post-hatch growth, very little work has been done on effects on behavior. We found that the time of hatching had sex-specific effects. Hatching times in females were negatively correlated with body weight, whereas in males, behaviors such as reaction to novelty and spatial learning were affected.As time of hatching is governed by various hormones, including thyroid hormone and corticosterone, we suggest that changes to the levels of these hormones could affect both hatching time and post-hatch phenotypes. Understanding these mechanisms better would be beneficial in terms of production, where batch homogeneity is important, in research on early experiences and the potential for maternal programming, and in evolutionary questions on trade-off between different life strateg...

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Section: Effects Of Domestication On Stress-related Gene Expressionsupporting

confidence: 90%

Section: Chicken Domesticationmentioning

confidence: 99%

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Domestication and early experiences in chickens: Behavior, stress and gene expression

Løtvedt¹

2017

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“…Cholesterol from high-density lipoprotein particles enters steroidogenic cells through diffusion that is facilitated by the SR-BI receptor (Reaven et al, 2001). Adrenal glands and testes have a unique cholesterol biosynthetic pathway to ensure cholesterol availability for steroidogenesis (Mitsche et al, 2015).Adrenocortical cells must respond rapidly to stress and to other signals that induce steroidogenesis within minutes after a stimulus (Bose et al, 2002;Fallahsharoudi et al, 2015). Many inhibitors of steroidogenesis cause a rapid increase in the cholesterol content of the adrenal glands or of cultured adrenocortical cells (Dibartolomeis et al, 1986;Lehoux and Lefebvre, 1991;Sbiera et al, 2015).…”

mentioning

confidence: 99%

ATR‐101 inhibits cholesterol efflux and cortisol secretion by ATP‐binding cassette transporters, causing cytotoxic cholesterol accumulation in adrenocortical carcinoma cells

Burns

Kerppola

2017

British J Pharmacology

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BACKGROUND AND PURPOSETo further the development of new agents for the treatment of adrenocortical carcinoma (ACC), we characterized the molecular and cellular mechanisms of cytotoxicity by the adrenalytic compound ATR-101 (PD132301-02). EXPERIMENTAL APPROACHWe compared the effects of ATR-101, PD129337, and ABC transporter inhibitors on cholesterol accumulation and efflux, on cortisol secretion, on ATP levels, and on caspase activation in ACC-derived cell lines. We examined the effects of these compounds in combination with methyl-β-cyclodextrin or exogenous cholesterol to determine the roles of altered cholesterol levels in the effects of these compounds. KEY RESULTSATR-101 caused cholesterol accumulation, ATP depletion, and caspase activation within 30 minutes after addition to ACC-derived cells, whereas PD129337 did not. Suppression of cholesterol accumulation by methyl-β-cyclodextrin or exogenous cholesterol, prevented ATP depletion and caspase activation by ATR-101. ATR-101 blocked cholesterol efflux and cortisol secretion, suggesting that it inhibited ABCA1, ABCG1, and MDR1 transporters. Combinations of ABCA1, ABCG1, and MDR1 inhibitors were also cytotoxic. Combinations of ATR-101 with inhibitors of ABCG1, MDR1, or mitochondrial functions had increased cytotoxicity. Inhibitors of steroidogenesis reduced ATP depletion by ATR-101, whereas U18666A enhanced cholesterol accumulation and ATP depletion together with ATR-101. ATR-101 repressed ABCA1, ABCG1, and IDOL transcription by mechanisms that were distinct from the mechanisms that caused cholesterol accumulation. CONCLUSIONS AND IMPLICATIONSInhibition of multiple ABC transporters and the consequent accumulation of cholesterol mediated the cytotoxicity of ATR-101. Compounds that replicate these effects in tumours are likely to be useful in the treatment of ACC. IntroductionControl of the levels of cholesterol (The term "cholesterol" is used to denote unesterified cholesterol in this paper) is essential for cell functions and viability (see Maxfield and Van Meer, 2010). The cholesterol levels in adrenocortical cells are affected by many pathways, some of which are unique to the adrenal cortex. Studies of anti-atherosclerosis agents have identified compounds that cause selective degeneration of the adrenal cortex (adrenalytic activity) in several species (Dominick et al., 1993;Reindel et al., 1994;Matsuo et al., 1996;Sliskovic et al., 1998;Tanaka et al., 1998). Here we have investigated the adrenalytic compound ATR-101, also known as PD132301-02, as a prospective agent for the treatment of adrenocortical carcinoma (ACC). We focused on ATR-101 because of its cytotoxicity in ACC-derived cells and its antixenograft and adrenalytic activities (Cheng et al., 2016). ACC is a rare cancer that has few treatment options. The adrenalytic compound mitotane is a first-line drug for ACC treatment despite its poor efficacy, unfavourable pharmacokinetics, severe side effects and potential drug interactions (Maiter et al., 2016). Clinical trials of molecularly targeted agents...

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“…As expected, allelic diversity between ancestral and domesticated animals has had a significant effect on transcriptomic changes, and production related tissues such as the liver, muscle and adipose tissue [35][36][37]. Also tissues affecting behaviour such as the adrenals and the brain have been of great interest [38][39][40][41][42]. Of particular importance is a study by Albert et al [38] in which four domestic mammals were compared in order to find convergent transcriptional genes or pathways to domestication.…”

Section: Domestication Geneticsmentioning

confidence: 99%

Chicken domestication : Effects of tameness on brain gene expression and DNA methylation

Bélteky¹

2016

Linköping Studies in Science and Technology. Dissertations

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Domestication greatly increases phenotypic variation in a short time span, with selection for a single phenotype and a plethora of associated phenotypic changes as an outcome of the process. The domestication process influences the underlying genomic architecture of a species, and the success and speed of the process is likely influenced by it. The main aims of my thesis was to study how domestication affects the brain of chickens: specifically changes in morphology, gene expression, and DNA methylation. Differences in gene expression and DNA methylation between White Leghorn and Red Junglefowl chickens were mapped, and inheritance of these patterns were quantified, indicating a faithful transmission of breed-specific epigenetic markers. Selection on the behavioral trait fearfulness, generated high and low fearful lines of Red Junglefowl. Both the parental population and the fifth selected generation were used for the analyses in this thesis. One experiment studied morphological changes in the brain and other vital organs, and found that relative total brain size increased in high fearful birds, as a consequence of an increase in cerebral hemisphere size in high fearful birds and not in low fearful birds. Also, the relative heart, liver, spleen and testis size increased in high fearful birds, indicating correlated morphological changes with selection for fearfulness. Two additional experiments examined differential gene expression in the hypothalamus and the anterior cerebral hemisphere. The hypothalamus differed in expression of genes with reproductive and immunological functions, whilst the cerebral hemisphere differed in expression of genes related to social behaviors and neurological functions especially those upregulated in low fearful birds. These results indicate the occurrence of tissue-and species-specific changes in gene expression as overlap with other domestication events were nearly nonexistent. A fourth experiment sought to associate the change in fear levels and gene expression differences with DNA methylation. Chromosomal regions with differential DNA methylation between high and low fearful birds were identified, and genes in these regions had annotated functions relevant to phenotypic differences between the selection lines. This thesis is the first to study the genetic alterations of domestication using the wild ancestor of an already domesticated species to repeat the domestication process selecting against fear of humans. The findings corroborate results from previous comparisons of wild and domestic animals, and further support the theory that rigorous selection for a behavioral trait can cause a cascade of genetic and epigenetic changes facilitating the domestication of a population. Populärvetenskaplig sammanfattningDomesticering, när en population djur anpassas till ett liv i fångenskap och nära kontakt med människor, är en process som under kort tid ger upphov till stora förändringar hos djuret under selektion, såsom skillnader i beteende, fysiologi, storlek, reproduktion och fä...

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Domestication Effects on Stress Induced Steroid Secretion and Adrenal Gene Expression in Chickens

Cited by 56 publications

References 82 publications

Domestication and early experiences in chickens: Behavior, stress and gene expression

Domestication and early experiences in chickens: Behavior, stress and gene expression

ATR‐101 inhibits cholesterol efflux and cortisol secretion by ATP‐binding cassette transporters, causing cytotoxic cholesterol accumulation in adrenocortical carcinoma cells

Chicken domestication : Effects of tameness on brain gene expression and DNA methylation

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