Some nuclear receptors have defined natural ligands, such as steroid hormones, thyroid hormones, retinoids, or vitamin D, but others have no identified ligand and are called orphan receptors. The finding that diverse compounds act as ligands for nuclear receptors and that some receptors have no apparent ligand led to the hypothesis that ancestral nuclear receptors were constitutive transcription factors that independently evolved the ability to bind ligand. 6,7 However, a second hypothesis posits that ancestral receptors were ligand-dependent transcription factors that evolved specificity for different ligands by gene duplication, mutation, and functional divergence. There are several lines of evidence that favors the latter hypothesis for the evolution of ligand binding in the steroid receptor family. First, the primary, secondary, and tertiary structures of the ligand-binding domain of different steroid receptors are highly similar. 8-11 Second, detailed sequence, structural, and functional analyses strongly support the hypothesis that the ancestral steroid receptor bound estrogens and specificity for other steroids evolved by serial and parallel duplications of the ancestral gene, mutation of nucleotides coding for specific amino acids, and structural and functional divergence of the paralogs. 12-14 Finally, steroid hormone receptors are nuclear receptors unique to the chordate lineage, indicating that they originated when the first chordates evolved.
Sex hormone-binding globulin (SHBG) is thought to mainly function as a transporter and reservoir for the estradiol and testosterone sex hormones. However it has also been demonstrated that SHBG can bind to a cell surface receptor (SHBG-R). The SHBG-R has not been completely characterized. A subset of steroids are able to bind to the SHBG/SHBG-R complex resulting in an activation of adenylyl cyclase and synthesis of the cAMP second messenger.  Hence the SHBG/SHBG-R complex appears to act as a transmembrane steroid receptor that is capable of transmitting signals to the interior of cells.
I have a lot of respect for Dr. Peter Lio — at least he is trying to learn about and raising awareness about TSW — but this article is wrong on a couple fronts, already pointed out in other comments. This article puts the blame on patients for misuse of topical steroids, but the reality is that many doctors (the majority it seems) either don’t know about or don’t believe TSW is real, and they ignore the risks of steroids noted in the drug inserts. Many patients end up with TSW after relying on their doctors’ guidance. We did.