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Relative adrenal insufficiency in mice deficient in 5α-reductase 1.
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.
Affiliation
  • Livingstone DE; EndocrinologyQueen's Medical Research Institute, University and British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK Dawn.Livingstone@ed.ac.uk.
  • Di Rollo EM; EndocrinologyQueen's Medical Research Institute, University and British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Yang C; EndocrinologyQueen's Medical Research Institute, University and British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Codrington LE; EndocrinologyQueen's Medical Research Institute, University and British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Mathews JA; EndocrinologyQueen's Medical Research Institute, University and British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Kara M; EndocrinologyQueen's Medical Research Institute, University and British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Hughes KA; EndocrinologyQueen's Medical Research Institute, University and British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Kenyon CJ; EndocrinologyQueen's Medical Research Institute, University and British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Walker BR; EndocrinologyQueen's Medical Research Institute, University and British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Andrew R; EndocrinologyQueen's Medical Research Institute, University and British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
J Endocrinol ; 222(2): 257-66, 2014 Aug.
Article in En | MEDLINE | ID: mdl-24872577
Patients with critical illness or hepatic failure exhibit impaired cortisol responses to ACTH, a phenomenon known as 'relative adrenal insufficiency'. A putative mechanism is that elevated bile acids inhibit inactivation of cortisol in liver by 5α-reductases type 1 and type 2 and 5ß-reductase, resulting in compensatory downregulation of the hypothalamic-pituitary-adrenal axis and adrenocortical atrophy. To test the hypothesis that impaired glucocorticoid clearance can cause relative adrenal insufficiency, we investigated the consequences of 5α-reductase type 1 deficiency in mice. In adrenalectomised male mice with targeted disruption of 5α-reductase type 1, clearance of corticosterone was lower after acute or chronic (eightfold, P<0.05) administration, compared with WT control 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 (43% lower, P<0.05) 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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Adrenal Insufficiency / Membrane Proteins Limits: Animals Language: En Journal: J Endocrinol Year: 2014 Document type: Article Country of publication: United kingdom

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Adrenal Insufficiency / Membrane Proteins Limits: Animals Language: En Journal: J Endocrinol Year: 2014 Document type: Article Country of publication: United kingdom