|Göteborgs universitets publikationer
Lack of regulation of 11beta-hydroxysteroid dehydrogenase type 1 during short-term manipulation of GH in patients with hypopituitarism.
Författare och institution:
Helga A Sigurjónsdóttir (-); Ruth Andrew (-); Roland H Stimson (-); Gudmundur Johannsson (Institutionen för medicin, avdelningen för invärtesmedicin); Brian R Walker (-)
European journal of endocrinology / European Federation of Endocrine Societies, 161 ( 3 ) s. 375-80
Artikel, refereegranskad vetenskaplig
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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP
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