Session: OR03-Glucocorticoids & Glucocorticoid Actions
Room 130 (Moscone Center)
Using microarray, RT-PCR and qPCR in a library of human tissue cDNA samples, we showed similar expression of ABCB1 and ABCC1 in kidney, liver and thymus; however, ABCC1 was more highly expressed than ABCB1 in peripheral blood mononuclear cells, skeletal muscle and adipose tissue. In differentiated SGBS cells, a human adipocyte cell line, mRNA and protein for ABCC1 were present, and ABCB1 was not expressed. This contrasts with murine subcutaneous and visceral adipose tissue and differentiated 3T3-L1 cells in which both ABCB1 and ABCC1 are expressed. Influx of 3H-corticosterone and 3H-cortisol into the intracellular fraction in SGBS cells was similar over 24h, however, efflux of corticosterone from cells was faster than that of cortisol at 4h (2.3-fold; p<0.05), 8h (2.8-fold; p<0.01) and 24h (3.2-fold; p<0.01). Incubation with the ABCC1 inhibitor MK-571 for 24h increased intracellular accumulation of 3H-corticosterone (3.5-fold; p<0.001) to a greater extent than 3H-cortisol (1.2-fold; p<0.001). In human adipose biopsies, ABCC1 transcript levels were higher in subcutaneous (n=6) than visceral (n=8) adipose tissue (1.6-fold; p<0.01) in lean individuals, and higher in subcutaneous (1.5-fold; p<0.01) but not visceral adipose in obese (n=8) compared with lean subjects.
Thus, expression of ABCC1 may render human adipose tissue more responsive to variations in cortisol than corticosterone, in contrast with CNS where expression of ABCB1 confers differential sensitivity to corticosterone. This mechanism may have evolved in humans to exploit the presence of two endogenous glucocorticoids and increase the plasticity of tissue-specific glucocorticoid action. In obesity, up-regulation of ABCC1 may protect subcutaneous, but not visceral, adipose tissue from corticosterone and thereby contribute to glucocorticoid-dependent visceral fat accumulation.
Nothing to Disclose: AIT, LER, DRD, MN, TMS, MZ, RA, BRW
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