Involvement of Glucocorticoids in the Reorganization ofthe 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.

Profile of cortisol, glycaemia, and blood parameters of American Bullfrog tadpoles Lithobates catesbeianus exposed to density and hypoxia stressors

“…Agents are released during the stress process, causing not only an increase or decrease in the immune response, but also a redistribution of immune cells throughout the entire body (Forbes et al 2006, Davis et al 2008. The metamorphosis involves a reorganization of the amphibian immune system (Rollins--Smith et al 1997) and the present study had metamorphosed animals in the high density. It is important to note that these physiological alterations consume energy and, from the moment that these stimuli become chronic, there is a tendency for the tertiary effects of stress to occur, i.e., a decrease in resistance and problems related to growth and development of these animals.…”

A dilution effect in the emerging amphibian pathogen Batrachochytrium dendrobatidis

“…Additionally, density and species richness may affect stress in A. boreas, altering their susceptibility to Bd. Stress hormones such as corticosterone affect amphibian immune function (41)(42)(43) and can be elevated in response to high larval density (44) and presumably in the presence of interspecific competition. Thus, our manipulations of larval density and species richness could have altered stress hormones, subsequently altering A. boreas' susceptibility to Bd.…”

Dietary protein restriction impairs growth, immunity, and disease resistance in southern leopard frog tadpoles

“…Because the hypothalamic-pituitary-interrenal (similar to the hypothalamic-pituitary-adrenal axis in mammals) and immune system function are coupled (Rollins-Smith 2001), it would not be surprising if increased corticosterone mediated either of the immune responses that we measured. Specifically, increased corticosterone reduces circulating lymphocytes in Xenopus tadpoles undergoing metamorphosis (Rollins-Smith et al 1997), which could ultimately inhibit PHA-induced skin swelling.…”