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Lack of regulation of 11 beta-hydroxysteroid dehydrogenase type 1 during short-term manipulation of GH in patients with hypopituitarism

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    Rights statement: Copyright 2009 European Society of Endocrinology This is an Open Access article distributed under the terms of the European Journal of Endocrinology's Re-use Licence.

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Original languageEnglish
Pages (from-to)375-80
Number of pages6
JournalEuropean Journal of Endocrinology
Volume161
Issue number3
DOIs
Publication statusPublished - Sep 2009

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 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1), thereby reducing cortisol regeneration in liver and adipose tissue. We aimed to measure acute effects of GH on 11 beta-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-H-2(4)-cortisol (d4-cortisol) infusion, urinary cortisol/cortisone metabolite ratios, liver 11 beta-HSD1 by appearance of plasma cortisol after oral cortisone, and 11 beta-HSD1 mRNA levels in subcutaneous adipose biopsies.

Results: GH withdrawal and reintroduction had no effect on 9.12,12-[H-2](3)-cortisol (d3-cortisol) appearance, urinary cortisol/cortisone metabolite ratios, initial appearance of cortisol after oral cortisone, or adipose 11 beta-HSD1 mRNA. GH withdrawal increased plasma cortisol 30-180 min after oral cortisone, increased d4-cortisol clearance. and decreased relative excretion of 5 alpha-reduced cortisol metabolites.

Conclusions: In this setting GH did not regulate 11 beta-HSD1 rapidly in vivo in humans. Altered cortisol metabolism with longer term changes in GH may reflect indirect effects on 11 beta-HSD1. These data do not suggest that glucocorticoid replacement doses need to be increased immediately after introducing GH therapy to compensate for reduced 11 beta-HSD1 activity, although dose adjustment may be required in the longer term.

    Research areas

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1, Adipose Tissue, White, Adult, Aged, Drug Dosage Calculations, Gene Expression Regulation, Enzymologic, Glucocorticoids, Hormone Replacement Therapy, Human Growth Hormone, Humans, Hydrocortisone, Hypopituitarism, Male, middle aged, Placebos, Time Factors, Withholding Treatment, Young Adult

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