RT Journal Article
SR Electronic
T1 Repeated stimulation of the HPA axis alters white blood cell counts without increasing oxidative stress or inflammatory cytokines in fasting elephant seal pups
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.31.437957
DO 10.1101/2021.03.31.437957
A1 David C. Ensminger
A1 Daniel E. Crocker
A1 Emily K. Lam
A1 N. Allen Kaitlin
A1 José Pablo Vázquez-Medina
YR 2021
UL http://biorxiv.org/content/early/2021/04/01/2021.03.31.437957.abstract
AB The hypothalamic-pituitary-adrenal (HPA) axis controls the release of glucocorticoids, which regulate immune and inflammatory function by modulating cytokines, white blood cells (WBCs), and oxidative stress via glucocorticoid receptor (GR) signaling. Although the response to HPA activation is well characterized in many species, little is known about the impacts of HPA activation during extreme physiological conditions in marine mammals. Hence, we challenged 18 simultaneously fasting and developing elephant seal pups with daily intramuscular injections of adrenocorticotropin (ACTH), a GR antagonist (RU486), or a combination (ACTH+RU486) for four days (4d). We collected blood at baseline, two hours (2h), and 4d after the beginning of treatment. ACTH and ACTH+RU486 elevated serum aldosterone and cortisol at 2h, with effects diminishing at 4d. RU486 alone induced a compensatory increase in aldosterone, but not cortisol, at 4d. ACTH decreased neutrophils at 2h while decreasing lymphocytes and increasing neutrophil:lymphocyte ratio at 4d. These effects were abolished by RU486. Despite alterations in WBCs, there was no effect of ACTH or RU486 on transforming growth factor-β or interleukin-6 levels; however, both cytokines decreased with the 4-d fasting progression. Similarly, ACTH did not impact protein oxidation, lipid peroxidation, or antioxidant enzymes, but plasma isoprostanes and catalase activity decreased while glutathione peroxidase increased with fasting progression. These data demonstrate differential acute (2h) and chronic (4d) modulatory effects of HPA activation on WBCs and that the chronic effect is mediated, at least in part, by GR. These results also underscore elephant seals’ resistance to potential oxidative stress derived from repeated HPA activation.Summary statement Many species experience oxidative stress and inflammation after repeated activation of the hypothalamic-pituitary-adrenal axis. We show that simultaneously fasting and developing elephant seals are resistant to repeated hypothalamic-pituitary-adrenal axis activation.Competing Interest StatementThe authors have declared no competing interest.