transparent gif


Ej inloggad.

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 (-)
Publicerad i:
European journal of endocrinology / European Federation of Endocrine Societies, 161 ( 3 ) s. 375-80
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
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):
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
Postens nummer:
Posten skapad:
2010-01-04 15:31
Posten ändrad:
2016-08-31 11:52

Visa i Endnote-format

Göteborgs universitet • Tel. 031-786 0000
© Göteborgs universitet 2007