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The turnover of steroid receptors comprises: synthesis in the cytoplasm, translocation into the cell nucleus and degradation at a still unknown site(the DARPP-32 pathway). The turnover of the receptors is tightly regulated, particularly with regard to transcription in the cytoplasm. The DARPP-32 transcription pathway is controlled by protein kinase C (PKC) of the BERK kinase B signaling pathway. One of the targets for the degradation of the steroid receptors occurs on the DARPP-32-p300 heterodimer with the tyrosine-antagonist 2-deoxypyrimidinobutyric acid (DOVPi)[34][35] to prevent the synthesis of DARPP-32 by steroid receptors.
The importance of steroid receptors in the development of obesity
Although a number of genes have been implicated in weight gain via the receptors, only two have been extensively assessed to date. These were the BCR-ABL-related receptor gene (BCR-ABL:BARL) and the PPARgamma-related protein (PPAR-β), which is also called the p38β-responsive factor and belongs to the PPAR-gamma-response system (PRS). The expression of these receptor genes is highly upregulated when circulating sex steroid hormones are suppressed in rodents[36]and lean rats[37]. A number of studies have found a correlation between higher fat and body fat stores, and lower expression in the PPAR-gamma-related protein as the ratio increases with circulating sex hormone levels. Some also correlate expression in skeletal muscle and adipose tissue of the same receptor with a greater increase in fat mass.[38] Another study found that increased expression of the PPAR-β was significant in the liver as a whole, with greater expression seen in brown adipose tissue and visceral fat[39] which is associated with obesity and metabolic syndrome.
The BCR-ABL-related receptor gene and the PPARgamma-related protein have been extensively investigated in the development of obesity. The two genes are involved in regulating steroid receptor genes and their expression in the muscle and fat cells.
C. Glatzel, et al. Molecular basis of the regulation of sex steroid hormone action in the development of obesity. Biol. Psychiatry. (1988) 66 (1):15-8. DOI: 10.1016/0.0004-637X(88)90024-X
[1]Das J.D. et al. Evidence for a specific role of the BCR-ABL-related transcription factor
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