The finding suggests, said Ingraham, that the mechanism would allow this nuclear orphan receptor to function much like a rheostat, elevating or diminishing gene activity.
Understanding the way in which SF-1 is regulated could offer insight into how the receptor responds to stress signals and initiates the production of sex steroids. "This molecule is at the cross-roads of how endocrine signaling is achieved," said Ingraham.
The finding could also lead to a recognition of a more general ligand-independent mechanism of action in nuclear receptors in some cancers.
Some hormonally induced cancers, such as of the breast and prostate, are initially sensitive to drugs that block hormone receptors, like the drug tamoxofen at the estrogen receptor. But sometimes these cancers go through stages of being resistant to hormone blockers, and it could be, said Ingraham, that the cancers are finding a way around the hormone-binding sites and signaling the receptors to produce estrogen or testosterone via another mechanism - perhaps the extracellular signal that culminates in phosphorylation.
On another level, the findings regarding SF-1 may have led researchers to a new appreciation for the complexity of nuclear receptor action and how these functions may have evolved. In recent years, scientists have determined that most nuclear receptors have phosphorylation sites, and that they play a secondary role to ligand binding. In these cases, the phosphorylation site, or AF-1 activation domain, is located at a distant location on the molecule from the ligand-binding site.