Depot-specific regulation of the conversion of cortisone to cortisol in human adipose tissue.

Abstract

OBJECTIVE:

Our main objective was to compare the regulation of cortisol production within omental (Om) and abdominal subcutaneous (Abd sc) human adipose tissue.

METHODS AND PROCEDURES:

Om and Abd sc adipose tissue were obtained at surgery from subjects with a wide range of BMI. Hydroxysteroid dehydrogenase (HSD) activity ((3)H-cortisone and (3)H-cortisol interconversion) and expression were measured before and after organ culture with insulin and/or dexamethasone.

RESULTS:

Type 1 HSD (HSD1) mRNA and reductase activity were mainly expressed within adipocytes and tightly correlated with adipocyte size within both depots. There was no depot difference in HSD1 expression or reductase activity, while cortisol inactivation and HSD2 mRNA expression (expressed in stromal cells) were higher in Om suggesting higher cortisol turnover in this depot. Culture with insulin decreased HSD reductase activity in both depots. Culture with dexamethasone plus insulin compared to insulin alone increased HSD reductase activity only in the Om depot. This depot-specific increase in reductase activity could not be explained by an alteration in HSD1 mRNA or protein, which was paradoxically decreased. However, in Om only, hexose-6-phosphate dehydrogenase (H6PDH) mRNA levels were increased by culture with dexamethasone plus insulin compared to insulin alone, suggesting that higher nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) production within the endoplasmic reticulum (ER) contributed to the higher HSD reductase activity.

DISCUSSION:

We conclude that in the presence of insulin, glucocorticoids cause a depot-specific increase in the activation of cortisone within Om adipose tissue, and that this mechanism may contribute to adipocyte hypertrophy and visceral obesity.

• Authors: Mi-Jeong Lee, Susan K Fried, Steven S Mundt, Yanxin Wang, Sean Sullivan, Alice Stefanni, Bruce L Daugherty, Anne Hermanowski-Vosatka
• Journal: Obesity (Silver Spring, Md.) (Obesity (Silver Spring)) Vol. 16 Issue 6 Pg. 1178-85 (Jun 2008) ISSN: 1930-7381 [Print] United States
• PMID: 18388900 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Glucocorticoids
• Hypoglycemic Agents
• Insulin
• RNA, Messenger
• Dexamethasone
• Oxidoreductases
• 11-beta-Hydroxysteroid Dehydrogenase Type 1
• 11-beta-Hydroxysteroid Dehydrogenase Type 2
• HSD11B1 protein, human
• HSD11B2 protein, human
• Cortisone
• Hydrocortisone

Topics

• 11-beta-Hydroxysteroid Dehydrogenase Type 1 (metabolism)
• 11-beta-Hydroxysteroid Dehydrogenase Type 2 (metabolism)
• Adipocytes (drug effects, metabolism)
• Adult
• Cortisone (metabolism)
• Dexamethasone (pharmacology)
• Female
• Glucocorticoids (pharmacology)
• Humans
• Hydrocortisone (metabolism)
• Hypoglycemic Agents (pharmacology)
• In Vitro Techniques
• Insulin (pharmacology)
• Male
• Middle Aged
• Omentum (cytology, metabolism)
• Oxidoreductases (metabolism)
• RNA, Messenger (metabolism)
• Subcutaneous Fat (cytology, metabolism)