TY - JOUR
T1 - Pharmacological characterization of central and peripheral type I and type II adrenal steroid receptors in the prairie vole, a glucocorticoid-resistant rodent
AU - Hastings, N. B.
AU - Orchinik, M.
AU - Aubourg, M. V.
AU - McEwen, B. S.
PY - 1999
Y1 - 1999
N2 - The prairie vole (Microtus ochrogaster) has recently been shown to be glucocorticoid resistant; that is, the prairie vole adrenal axis is refractory to dexamethasone challenge, and highly elevated basal corticosterone titers occur without apparent pathophysiology. This study investigates the physiological correlates of glucocorticoid resistance in the prairie vole. We provide a detailed pharmacological characterization of intracellular type I and type II adrenal steroid receptors in peripheral tissues and the hippocampus of the prairie vole and the Sprague Dawley rat, a corticosensitive rodent. Adrenalectomy markedly reduces, but does not eliminate, circulating glucocorticoids in the prairie vole. Nonetheless, molecular, cellular, and physiological assays indicate adrenal insufficiency; salt appetite and dentate gyrus granule cell death are increased after adrenalectomy, suggesting vacancy of the high affinity type I subtype of central adrenal steroid receptor. Analysis of adrenal steroid receptor binding constants and selectivity for endogenous and synthetic steroids in the vole and rat indicated that the vole type I receptor is nearly identical to that of the rat in brain and periphery. However, voles demonstrated a 2-fold lower type I receptor binding density in colon and hippocampus compared with that in rats. The vole type II receptor bound the endogenous glucocorticoid corticosterone with an 8- to 10-fold lower affinity than the rat type II receptor and was expressed in lower densities in thymus and hippocampus. These data indicate physiological adaptations in the prairie vole adrenal axis consistent with other glucocorticoid-resistant species, such as the guinea pig and squirrel monkey.
AB - The prairie vole (Microtus ochrogaster) has recently been shown to be glucocorticoid resistant; that is, the prairie vole adrenal axis is refractory to dexamethasone challenge, and highly elevated basal corticosterone titers occur without apparent pathophysiology. This study investigates the physiological correlates of glucocorticoid resistance in the prairie vole. We provide a detailed pharmacological characterization of intracellular type I and type II adrenal steroid receptors in peripheral tissues and the hippocampus of the prairie vole and the Sprague Dawley rat, a corticosensitive rodent. Adrenalectomy markedly reduces, but does not eliminate, circulating glucocorticoids in the prairie vole. Nonetheless, molecular, cellular, and physiological assays indicate adrenal insufficiency; salt appetite and dentate gyrus granule cell death are increased after adrenalectomy, suggesting vacancy of the high affinity type I subtype of central adrenal steroid receptor. Analysis of adrenal steroid receptor binding constants and selectivity for endogenous and synthetic steroids in the vole and rat indicated that the vole type I receptor is nearly identical to that of the rat in brain and periphery. However, voles demonstrated a 2-fold lower type I receptor binding density in colon and hippocampus compared with that in rats. The vole type II receptor bound the endogenous glucocorticoid corticosterone with an 8- to 10-fold lower affinity than the rat type II receptor and was expressed in lower densities in thymus and hippocampus. These data indicate physiological adaptations in the prairie vole adrenal axis consistent with other glucocorticoid-resistant species, such as the guinea pig and squirrel monkey.
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U2 - 10.1210/endo.140.10.7050
DO - 10.1210/endo.140.10.7050
M3 - Article
C2 - 10499499
AN - SCOPUS:0033304871
SN - 0013-7227
VL - 140
SP - 4459
EP - 4469
JO - Endocrinology
JF - Endocrinology
IS - 10
ER -