Abstract
Following extensive suprasellar operations for excision of hypothalamic tumors, some
patients develop morbid obesity despite receiving replacement doses of glucocorticoids.
Urine analysis of cortisol and cortisone metabolites show that 11-OH/11-oxo ratios
are significantly higher in patients with hypothalamic obesity, indicating enhanced
11β-HSD1 activity. This correlates with the visceral-to-subcutaneous fat ratio. The
consequence of increased 11β-HSD1 activity and a shift of the steroid inter-conversion
towards cortisol may contribute to the effects of the latter in adipose tissue. The
message from the hypothalamus to adipocyte 11β-HSD-1 involves hormones, the sympathetic
nervous system and cytokines. CRH and ACTH downregulate 11β-HSD-1 activity and induce
lipolysis. Tumor necrosis factor-α and interleukin-1β upregulate 11β-HSD-1 expression
and activity, while enhancing lipolysis. The sympathetic nervous system exerts its
effects through β-adrenergic upregulation and α-adrenergic downregulation of 11β-HSD-1
activity. Inhibition of 11β-HSD-1 suppresses preadipocyte differentiation into mature
adipocytes, and may provide a therapeutic tool.
Key words
Hypothalamus - Obesity - 11β-hydroxysteroid dehydrogenase - Adipocyte
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Ze’ev Hochberg M. D., DSc
Meyer Children’s Hospital
POB 9602 · Haifa 31096 · Israel ·
Fax: + 972 (4) 854 21 57
Email: z_hochberg@rambam.health.gov.il
