ArticleThe Journal of endocrinology2014
Relative adrenal insufficiency in mice deficient in 5α-reductase 1.
Article in The Journal of endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Absence of Interaction Between 5α-Reductase Inhibitors and Glucocorticoids on Incidence of Myocardial Infarction in People With Type 2 Diabetes.Diabetes, obesity & metabolism · 2026Article
- Steroid 5α-reductases in the brain: From neurosteroidogenesis to therapeutic implications.Frontiers in neuroendocrinology · 2026Review
- Cardiovascular safety of 5α-reductase inhibitors in people with benign prostatic hyperplasia and type 2 diabetes: a propensity score-matched analysis.European heart journal. Cardiovascular pharmacotherapy · 2026Article
- Bone marrow-derived mesenchymal stem cell ameliorates post-stroke enterobacterial translocation through liver-gut axis.Stroke and vascular neurology · 2025Article
- Neurosteroids: a lifelong impact on brain health.Frontiers in behavioral neuroscience · 2025Review
- ATP-binding cassette family C member 1 constrains metabolic responses to high-fat diet in male mice.The Journal of endocrinology · 2024Article
- Chronic Aroclor 1260 exposure alters the mouse liver proteome, selenoproteins, and metals in steatotic liver disease.Environmental toxicology and pharmacology · 2024Article
- Grape Polyphenols May Prevent High-Fat Diet-Induced Dampening of the Hypothalamic-Pituitary-Adrenal Axis in Male Mice.Journal of the Endocrine Society · 2023Article
- Pseudohypoadrenalism, a subclinical cortisol metabolism disorder in hyperuricemia.Frontiers in endocrinology · 2023Article
- Altered Cortisol Metabolism Increases Nocturnal Cortisol Bioavailability in Prepubertal Children With Type 1 Diabetes Mellitus.Frontiers in endocrinology · 2021Article
- Unravelling the role of epigenetics in reproductive adaptations to early-life environment.Nature reviews. Endocrinology · 2020Review
- Role of Hepatic Glucocorticoid Receptor in Metabolism in Models of 5αR1 Deficiency in Male Mice.Endocrinology · 2019Article
- Dysregulation of Cortisol Metabolism in Equine Pituitary Pars Intermedia Dysfunction.Endocrinology · 2018Article
- Hypothalamus-Pituitary-Adrenal Dysfunction in Cholestatic Liver Disease.Frontiers in endocrinology · 2018Review
- Hyperactivity of Hypothalamic-Pituitary-Adrenal Axis Due to Dysfunction of the Hypothalamic Glucocorticoid Receptor in Sigma-1 Receptor Knockout Mice.Frontiers in molecular neuroscience · 2017Article
- Metabolic dysfunction in female mice with disruption of 5α-reductase 1.The Journal of endocrinology · 2017Article
- Adverse effects of 5α-reductase inhibitors: What do we know, don't know, and need to know?Reviews in endocrine & metabolic disorders · 2015Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
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 5β-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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