title: Muscle transcriptome response to ACTH administration in a free-ranging marine mammal.
abstract: While much of our understanding of stress physiology is derived from biomedical studies, little is known about the downstream molecular consequences of adaptive stress responses in free-living animals. We examined molecular effectors of the stress hormones cortisol and aldosterone in the northern elephant seal, a free-ranging study system in which extreme physiological challenges and cortisol fluctuations are a routine part of life history. We stimulated the neuroendocrine stress axis by administering exogenous adrenocorticotropic hormone (ACTH) and examined the resultant effects by measuring corticosteroid hormones, metabolites, and gene expression before, during, and following administration. ACTH induced an elevation in cortisol, aldosterone, glucose, and fatty acids within 2 h, with complete recovery observed within 24 h of administration. The global transcriptional response of elephant seal muscle tissue to ACTH was evaluated by transcriptomics and involved upregulation of a highly coordinated network of conserved glucocorticoid (GC) target genes predicted to promote metabolic substrate availability without causing deleterious effects seen in laboratory animals. Transcriptional recovery from ACTH was characterized by downregulation of GC target genes and restoration of cell proliferation, metabolism, and tissue maintenance pathways within 24 h. Differentially expressed genes included several adipokines not previously described in muscle, reflecting unique metabolic physiology in fasting-adapted animals. This study represents one of the first transcriptome analyses of cellular responses to hypothalamic-pituitary-adrenal axis stimulation in a free-living marine mammal and suggests that compensatory, tissue-sparing mechanisms may enable marine mammals to maintain cortisol and aldosterone sensitivity while avoiding deleterious long-term consequences of stress.
authors.affiliation: Department of Biology, Sonoma State University, Rohnert Park, California; khudyako@sonoma.edu.
authors.forename: Jane I
authors.initials: JI
authors.lastname: Khudyakov
authors.affiliation: Conservation and Biological Research Program, National Marine Mammal Foundation, San Diego, California;
authors.forename: Cory D
authors.initials: CD
authors.lastname: Champagne
authors.affiliation: Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan; and.
authors.forename: Likit
authors.initials: L
authors.lastname: Preeyanon
authors.affiliation: School of Natural Sciences, University of California, Merced, Merced, California.
authors.forename: Rudy M
authors.initials: RM
authors.lastname: Ortiz
authors.affiliation: Department of Biology, Sonoma State University, Rohnert Park, California;
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Crocker
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D059001:Aquatic Organisms / Q000235:genetics / Q000502:physiology; D004703:Endocrine System / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D008297:Male; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism*; D046048:Seals, Earless / Q000235:genetics / Q000502:physiology*; D017423:Sequence Analysis, RNA; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D059467:Transcriptome / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000324:Adrenocorticotropic Hormone
keywords: ACTH; corticosteroid; muscle; seal; transcriptome