Lack of regulation of 11beta-hydroxysteroid dehydrogenase type 1 during short-term manipulation of GH in patients with hypopituitarism.
| العنوان: | Lack of regulation of 11beta-hydroxysteroid dehydrogenase type 1 during short-term manipulation of GH in patients with hypopituitarism. |
|---|---|
| المؤلفون: | Sigurjónsdóttir, Helga A, 1964, Andrew, Ruth, Stimson, Roland H, Johannsson, Gudmundur, 1960, Walker, Brian R |
| المصدر: | European journal of endocrinology / European Federation of Endocrine Societies. 161(3):375-80 |
| مصطلحات موضوعية: | MEDICAL AND HEALTH SCIENCES, MEDICIN OCH HÄLSOVETENSKAP, 11-beta-Hydroxysteroid Dehydrogenase Type 1, genetics, metabolism, Adipose Tissue, White, drug effects, Adult, Aged, Drug Dosage Calculations, Gene Expression Regulation, Enzymologic, Glucocorticoids, administration & dosage, therapeutic use, Hormone Replacement Therapy, Human Growth Hormone, Humans, Hydrocortisone, blood, urine, Hypopituitarism, drug therapy, Male, Middle Aged, Placebos, Time Factors, Withholding Treatment, Young Adult |
| الوصف: | 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. |
| الوصول الحر: | https://gup.ub.gu.se/publication/105333Test |
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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. ) Array ( [Name] => URL [Label] => Access URL [Group] => URL [Data] => <link linkTarget="URL" linkTerm="https://gup.ub.gu.se/publication/105333" linkWindow="_blank">https://gup.ub.gu.se/publication/105333</link> ) |
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