Transcriptome analysis of the hypothalamic-pituitary-adrenal axis in the experimentally domesticated fox

Variation in activity of the hormonal stress response, or hypothalamic-pituitary-adrenal (HPA) axis, has been associated with different personality traits and coping styles in humans and animals, while its dysregulation has been implicated in psychological disorders. The molecular basis of HPA axis regulation, however, is not yet well understood. Here, foxes selectively bred for tameness or aggression are used as a model to investigate differences in regulation of the HPA axis. Activity of this axis is markedly reduced in tame compared to aggressive foxes, with reduced levels of HPA axis hormones such as adrenocorticotrophic hormone (ACTH) and cortisol both basally and in response to a stressor. Gene expression differences were analyzed using RNA sequencing in the anterior pituitary and adrenal glands of foxes from the tame and aggressive lines, and variant analysis was performed on RNA reads from hypothalamus, anterior pituitary, and adrenal tissues from the same foxes. Pituitary analysis revealed expression differences in genes related to exocytosis and cellular signaling; adrenals analysis identified differences in similar pathways, in addition to genes related to fatty acid and cholesterol synthesis. Variant analysis also implicated cell signaling and exocytosis, as well as ion transport and DNA damage repair. These findings suggest the importance of regulation of hormone release in the control of ACTH and cortisol levels. They also suggest that metabolism of precursors to cortisol, such as fatty acids and cholesterol, may be of greater importance in HPA axis regulation than synthesis of cortisol itself. Finally, in conjunction with previous genomic findings, they suggest an association between DNA repair mechanisms and selection for tameness. These findings provide possible new lines of investigation into biological underpinnings of the phenotypic differences between the tame and aggressive lines of foxes. More broadly, as the tame foxes are considered experimentally domesticated, the findings from this project may prove applicable to HPA axis regulation differences associated with domestication in other species. Additionally, a deeper understanding of HPA axis regulation and dysregulation may be applicable both to variation in the normal population, particularly as related to behavioral traits such as coping styles, and to a number of psychiatric disorders in humans, as well as to behavioral disorders in other species, such as dogs.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Animal Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2017

Author dc:creator

• Hekman, Jessica Perry

Contributors dc:contributor

• Kukekova, Anna V.
• Beever, Jonathan
• Bell, Allison
• Raetzman, Lori
• Stubbs, Lisa

• Ribonucleic acid sequence (RNA-seq)
• Stress
• Pituitary
• Adrenals
• Hypothalamic-pituitary-adrenal (HPA)

Statement dc:rights

• Copyright 2017 Jessica Perry Hekman

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/98347

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/98347