| Autor: |
Livingstone, Dawn E. W., Di Rollo, Emma M., Yang, Chenjing, Codrington, Lucy E., Mathews, John A., Kara, Madina, Hughes, Katherine A., Kenyon, Christopher J., Walker, Brian R., Andrew, Ruth |
| Předmět: |
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| Zdroj: |
Journal of Endocrinology; Aug2014, Vol. 222 Issue 2, p257-266, 10p |
| Abstrakt: |
Patients with critical illness or hepatic failure exhibit impaired cortisol responses to ACTH, a phenomenon known as'relative adrenal insufficiency'. A putative mechanism isthat elevated bile acids inhibit inactivation of cortisol in liver by 5a-reductasestype 1 and type 2 and 5ß-reductase, resulting in compensatory downregulation of the hypothalamic-pituitaryadrenal axis and adrenocortical atrophy. To test the hypothesis that impaired glucocorticoid clearance can cause relative adrenal insufficiency, we investigated the consequences of 5a-reductasetype 1 deficiency in mice. In adrenalectomised male mice with targeted disruption of 5a-reductasetype 1, clearance of corticosterone was lower after acute or chronic (eightfold, P<0.05) administration, compared with WTcontrol mice. In intact 5α-reductase-deficient male mice, although resting plasma corticosterone levels were maintained, corticosterone responses were impaired after ACTH administration (26% lower, P<0.05), handling stress (2.5-fold lower, P<0.05) and restraint stress ( 4 3% lower, P < 0 . 0 5 ) compared with WT mice. mRNA levels of Nr3c1 (glucocorticoid receptor), Crh and Avp in pituitary or hypothalamus were altered, consistent with enhanced negative feedback. These findings confirm that impaired peripheral clearance of glucocorticoids can cause 'relative adrenal insufficiency' in mice, an observation with important implications for patients with critical illness or hepatic failure, and for patients receiving 5α-reductase inhibitors for prostatic disease. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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