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11 beta-Hydroxysteroid dehydrogenase activity in hypothalamic obesity.
Dov Tiosano1, Israel Eisentein, Daniela Militianu
1Departments of Pediatrics, Meyer Children's Hospital, Haifa 31096, Israel.
The Journal of Clinical Endocrinology and Metabolism
|January 10, 2003
Summary
Hypothalamic obesity after surgery may be linked to increased conversion of inactive to active glucocorticoids. This enhanced 11 beta-hydroxysteroid dehydrogenase 1 (HSD1) activity shifts the balance towards cortisol, potentially driving obesity.
Area of Science:
- Endocrinology
- Metabolic Disorders
- Neuroendocrinology
Background:
- Patients with hypothalamic lesions, particularly after surgery for tumor removal, can develop Cushing-like obesity despite glucocorticoid replacement therapy.
- This suggests an underlying mechanism beyond simple hormone replacement dosage.
Purpose of the Study:
- To investigate the hypothesis that increased target tissue conversion of inactive 11-ketosteroids to active 11 beta-hydroxy glucocorticoids contributes to obesity in patients with hypothalamic lesions.
- To assess the activity of 11 beta-hydroxysteroid dehydrogenase (HSD) in patients with hypothalamic obesity and secondary adrenal insufficiency.
Main Methods:
- Studied 10 patients with hypothalamic obesity and secondary adrenal insufficiency and 6 control Addisonian patients on glucocorticoid replacement.
- Administered a single oral dose of hydrocortisone acetate and collected 24-hour urine samples.
- Assessed 11 beta-hydroxysteroid dehydrogenase (HSD) activity by measuring ratios of cortisol (F) to cortisone (E) and their metabolites in urine.
Main Results:
- Patients with hypothalamic obesity exhibited significantly higher urinary 11-hydroxy/11-oxo steroid ratios, indicating increased HSD activity.
- While the 11-OH/11-oxo ratios did not correlate with obesity severity, a correlation was found between conjugated F/E ratios and visceral to subcutaneous fat distribution.
- These findings suggest a shift in interconversion favoring cortisol production.
Conclusions:
- Increased 11 beta-HSD1 activity and the resulting shift towards cortisol may contribute to obesity in patients with hypothalamic lesions.
- Deficiency of hypothalamic messengers post-surgery could induce paracrine/autocrine effects of enhanced glucocorticoid activity via up-regulated 11 beta-HSD1.