title: Involvement of glucocorticoids in the reorganization of the amphibian immune system at metamorphosis.
abstract: In recent years, integrative animal biologists and behavioral scientists have begun to understand the complex interactions between the immune system and the neuroendocrine system. Amphibian metamorphosis offers a unique opportunity to study dramatic hormone-driven changes in the immune system in a compressed time frame. In the South African clawed frog, Xenopus laevis, the larval pattern of immunity is distinct from that of the adult, and metamorphosis marks the transition from one pattern to the other. Climax of metamorphosis is characterized by significant elevations in thyroid hormones, glucocorticoid hormones, and the pituitary hormones, prolactin and growth hormone. Previously, we and others have shown that elevated levels of unbound glucocorticoid hormones found at climax of metamorphosis are associated with a natural decline in lymphocyte numbers, lymphocyte viability, and mitogen-induced proliferation. Here we present evidence that the mechanism for loss of lymphocytes at metamorphosis is glucocorticoid-induced apoptosis. Inhibition of lymphocyte function and loss of lymphocytes in the thymus and spleen are reversible by in vitro or in vivo treatment with the glucocorticoid receptor antagonist, RU486, whereas the mineralocorticoid receptor antagonist, RU26752, is poorly effective. These observations support the hypothesis that loss of larval lymphocytes and changes in lymphocyte function are due to elevated concentrations of glucocorticoids that remove unnecessary lymphocytes to allow for development of immunological tolerance to the new adult-specific antigens that appear as a result of metamorphosis.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2580, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Rollins-Smith
authors.forename: K S
authors.initials: KS
authors.lastname: Barker
authors.forename: A T
authors.initials: AT
authors.lastname: Davis
mesh_terms: D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D003345:Corticosterone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008675:Metamorphosis, Biological / Q000187:drug effects; D015735:Mifepristone / Q000494:pharmacology*; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014982:Xenopus laevis
chemical_list: D005938:Glucocorticoids; D006727:Hormone Antagonists; D013148:Spironolactone; D015735:Mifepristone; D000450:Aldosterone; C047175:7-propyl spirolactone; D003345:Corticosterone