Upregulation of ß3-adrenoceptors-a general marker of and protective mechanism against hypoxia?

ß3-Adrenoceptors exhibit a restricted expression pattern, particularly in humans. However, they have been found to be upregulated in various cancers and under several conditions associated with hypoperfusion such as congestive heart failure and diabetes for instance in the heart and other tissues. These conditions are frequently associated with hypoxia. Furthermore, direct induction of hypoxia has consistently been reported to cause upregulation of ß3-adrenoceptors across various tissues of multiple species including humans, rats, dogs, and fish. While a canonical hypoxia-response element in the promoter of the human ß3-adrenoceptor gene may play a role in this, no such sequence was found in rodent homologs. Moreover, not all upregulation of ß3-adrenoceptor protein is accompanied by increased expression of corresponding mRNA, indicating that the upregulation may involve factors other than transcriptional changes. We propose that upregulation of ß3-adrenoceptors at the mRNA and/or protein level is a general marker of hypoxic conditions. Moreover, it may be an additional pathway whereby cells and tissues adapt to reduced oxygen levels.