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• W2000627237 startingPage "1322" @default.
• W2000627237 abstract "Steroidogenic factor-1 (SF-1), has emerged as a critical nuclear receptor regulating development and differentiation at several levels of the hypothalamic-pituitary-steroidogenic axis. Although many coregulatory factors have been shown to physically and functionally interact with SF-1, the relative importance of these interactions in SF-1 target tissues has not been thoroughly established. In this study we assessed roles of steroid receptor coactivator-1 (SRC-1) in hypothalamic-pituitary-adrenal (HPA) axis function using SRC-1-deficient (SRC-1−/−) mice in the absence or presence of SF-1 haploinsufficiency. Surprisingly, SRC-1 deficiency did not alter baseline HPA axis function or the acute rise in corticosterone after ACTH administration and failed to exacerbate adrenocortical dysfunction in SF-1+/− mice. However, after exposure to paradigms of acute and chronic stress, SRC-1−/− mice exhibited an elevation in serum corticosterone despite normal (nonsuppressed) ACTH, suggesting an increase in adrenal sensitivity as well as a concomitant defect in glucocorticoid-mediated feedback inhibition of the HPA axis. An examination of potential compensatory mechanism(s) revealed an increase in adrenal weight, selective elevation of melanocortin 2 receptor mRNA, and a coincident increase in SRC-2 and SRC-3 expression in SRC-1−/− adrenals. A reduction in blood glucose was observed in SRC-1−/− mice after chronic stress, consistent with a generalized state of glucocorticoid resistance. Dexamethasone suppression tests confirmed a weakened ability of glucocorticoids to 1) elevate serum glucose levels and induce hepatic phosphoenolpyruvate carboxykinase transcription and 2) suppress pituitary proopiomelanocortin transcript levels in SRC-1−/− animals. Collectively, these data are consistent with an indispensable role for SRC-1 in mediating actions of glucocorticoids in pituitary and liver." @default.
• W2000627237 created "2016-06-24" @default.
• W2000627237 creator A5038089054 @default.
• W2000627237 creator A5041163845 @default.
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• W2000627237 creator A5073697965 @default.
• W2000627237 date "2006-03-01" @default.
• W2000627237 modified "2023-09-27" @default.
• W2000627237 title "Steroid Receptor Coactivator-1-Deficient Mice Exhibit Altered Hypothalamic-Pituitary-Adrenal Axis Function" @default.
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• W2000627237 doi "https://doi.org/10.1210/en.2005-0751" @default.
• W2000627237 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16339206" @default.
• W2000627237 hasPublicationYear "2006" @default.
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