Regulation and Variability of Signaling by Nuclear Receptors

Signaling by nuclear receptors is regulated at various levels (Fig. 4.12). The following are important regulatory attack points  

A main determinant of nuclear receptor signaling is the concentration of the ligand available for binding. The ligand concentration can be regulated in many ways (for details see textbooks on hormone action)  

The latter point is of importance in the hypothalamus-pituitary system of the brain, where feedback inhibition at various levels is used to prevent overproduction of, e.g., steroid hormones or the T3 hormone. 

The phosphorylation of nuclear receptors on Ser/Thr residues is a key mechanism for the coupling of nuclear receptor signaling to other signaling pathways of the cell. Many nuclear receptors are isolated as phosphoproteins, and their phosphorylation provides a means for ligand-independent activation and regulation. The steroid 

In addition to the receptors themselves, the nuclear receptor coactivators have also been found to be targets of regulatory phosphorylation events. 

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