Greater replication and differentiation of preadipocytes in inherited corticosteroid-binding globulin deficiency

• Published in: American journal of physiology: endocrinology and metabolism 2003-05, Vol.284 (5), p.E1049-E1054
• Main Authors: Joyner, J. M, Hutley, L. J, Bachmann, A. W, Torpy, D. J, Prins, J. B
• Format: Article
• Language: English
• Subjects: 11-beta-Hydroxysteroid Dehydrogenase Type 2; 11-beta-Hydroxysteroid Dehydrogenases; Adipocytes - pathology; Adult; Aged; Cell Differentiation; Cell Division; Cells, Cultured; Gene Expression; Humans; Hydroxysteroid Dehydrogenases - metabolism; Male; Metabolism, Inborn Errors - genetics; Metabolism, Inborn Errors - metabolism; Metabolism, Inborn Errors - pathology; Middle Aged; Mutation; Receptors, Glucocorticoid - metabolism; Reference Values; Stem Cells - pathology; Transcortin - deficiency; Transcortin - genetics
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00262.2002

1  Department of Medicine, Redland Hospital, Cleveland, Queensland 4163; 2  Department of Medicine, University of Queensland, and 3  Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Woolloongabba, Queensland 4102; and 4  Greenslopes Private Hospital, Greenslopes, Queensland 4120, Australia Glucocorticoids are pivotal for adipose tissue development. Rodent studies suggest that corticosteroid-binding globulin (CBG) modulates glucocorticoid action in adipose tissue. In humans, both genetic CBG deficiency and suppressed CBG concentrations in hyperinsulinemic states are associated with obesity. We hypothesized that CBG deficiency in humans modulates the response of human preadipocytes to glucocorticoids, predisposing them to obesity. We compared normal preadipocytes with subcultured preadipocytes from an individual with the first ever described complete deficiency of CBG due to a homozygous null mutation. CBG-negative preadipocytes proliferated more rapidly and showed greater peroxisome proliferator-activated receptor- -mediated differentiation than normal preadipocytes. CBG was not expressed in normal human preadipocytes. Glucocorticoid receptor number and binding characteristics and 11 -hydroxysteroid dehydrogenase activity were similar for CBG-negative and normal preadipocytes. We propose that the increased proliferation and enhanced differentiation of CBG-negative preadipocytes may promote adipose tissue deposition and explain the obesity seen in individuals with genetic CBG deficiency. Furthermore, these observations may be relevant to obesity occurring with suppressed CBG concentrations associated with hyperinsulinemia. adipose tissue; glucocorticoid; human; obesity; peroxisome proliferator-activated receptor-