Involvement of Glucocorticoids in the Reorganization of the Amphibian Immune System at Metamorphosis

In recent years, integrative animal biologists and behavioral scientists have begun to understandthe complex interactions between the immune system and the neuroendocrine system.Amphibian metamorphosis offers a unique opportunity to study dramatic hormone-drivenchanges 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 metamorphosismarks the transition from one pattern to the other. Climax of metamorphosis ischaracterized by significant elevations in thyroid hormones, glucocorticoid hormones, and thepituitary hormones, prolactin and growth hormone. Previously, we and others have shown thatelevated levels of unbound glucocorticoid hormones found at climax of metamorphosis are associatedwith a natural decline in lymphocyte numbers, lymphocyte viability, and mitogen-inducedproliferation. Here we present evidence that the mechanism for loss of lymphocytes atmetamorphosis is glucocorticoid-induced apoptosis. Inhibition of lymphocyte function andloss of lymphocytes in the thymus and spleen are reversible by in vitro or in vivo treatmentwith the glucocorticoid receptor antagonist, RU486, whereas the mineralocorticoid receptorantagonist, RU26752, is poorly effective. These observations support the hypothesis that lossof larval lymphocytes and changes in lymphocyte function are due to elevated concentrationsof glucocorticoids that remove unnecessary lymphocytes to allow for development of immunologicaltolerance to the new adult-specific antigens that appear as a result of metamorphosis.