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Lack of regulation ...
Lack of regulation of 11beta-hydroxysteroid dehydrogenase type 1 during short-term manipulation of GH in patients with hypopituitarism.
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Sigurjónsdóttir, Helga A, 1964 (author)
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Andrew, Ruth (author)
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Stimson, Roland H (author)
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- Johannsson, Gudmundur, 1960 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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Walker, Brian R (author)
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(creator_code:org_t)
- 2009
- 2009
- English.
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In: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 161:3, s. 375-80
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- OBJECTIVE: Evidence from long-term clinical studies measuring urinary steroid ratios, and from in vitro studies, suggests that GH administered for longer than 2 months down-regulates 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), thereby reducing cortisol regeneration in liver and adipose tissue. We aimed to measure acute effects of GH on 11beta-HSD1 in liver and adipose tissue in vivo, including using a stable isotope tracer. DESIGN: Observational studies of GH withdrawal and reintroduction in patients with hypopituitarism. METHODS: Twelve men with benign pituitary disease causing GH and ACTH deficiency on stable replacement therapy for >6 months were studied after GH withdrawal for 3 weeks, and after either placebo or GH injections were reintroduced for another 3 weeks. We measured cortisol kinetics during 9,11,12,12-(2)H(4)-cortisol (d4-cortisol) infusion, urinary cortisol/cortisone metabolite ratios, liver 11beta-HSD1 by appearance of plasma cortisol after oral cortisone, and 11beta-HSD1 mRNA levels in subcutaneous adipose biopsies. RESULTS: GH withdrawal and reintroduction had no effect on 9,12,12-[(2)H](3)-cortisol (d3-cortisol) appearance, urinary cortisol/cortisone metabolite ratios, initial appearance of cortisol after oral cortisone, or adipose 11beta-HSD1 mRNA. GH withdrawal increased plasma cortisol 30-180 min after oral cortisone, increased d4-cortisol clearance, and decreased relative excretion of 5alpha-reduced cortisol metabolites. CONCLUSIONS: In this setting, GH did not regulate 11beta-HSD1 rapidly in vivo in humans. Altered cortisol metabolism with longer term changes in GH may reflect indirect effects on 11beta-HSD1. These data do not suggest that glucocorticoid replacement doses need to be increased immediately after introducing GH therapy to compensate for reduced 11beta-HSD1 activity, although dose adjustment may be required in the longer term.
Keyword
- 11-beta-Hydroxysteroid Dehydrogenase Type 1
- genetics
- metabolism
- Adipose Tissue
- White
- drug effects
- metabolism
- Adult
- Aged
- Drug Dosage Calculations
- Gene Expression Regulation
- Enzymologic
- drug effects
- Glucocorticoids
- administration & dosage
- therapeutic use
- Hormone Replacement Therapy
- Human Growth Hormone
- therapeutic use
- Humans
- Hydrocortisone
- blood
- urine
- Hypopituitarism
- blood
- drug therapy
- genetics
- urine
- Male
- Middle Aged
- Placebos
- Time Factors
- Withholding Treatment
- Young Adult
Publication and Content Type
- ref (subject category)
- art (subject category)
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