Hormone agonists

[basophilic]

Say you have a nuclear receptor R to which steroid hormone H binds. In an in vitro culture, you add a synthetic compound X that binds with a 1000 times higher affinity to the active (H-binding) site of R; this is observed to INCREASE mRNA transcription of the genes upregulated by H. So a few questions: 1) Is this actually a plausible phenomenon? 2) From the cell's point of view, it probably feels there's a lot of H inside the nucleus (even though there's not), right? So would this mean the cell would stop importing further H? In other words, would the H agonist (X) act exactly like H in terms of both activity and regulation?

---

Members don't see this ad.

 

[kingtal0n]

I am under the impression that most steroid hormones are hydrophobic enough to pass directly through to the nucleus without transport, where they can activate any number of receptors with varying affinity.

I would say that if the receptor R is part of a protein guarding the transcription of an mRNA molecule then of course H or X could remove this inhibiting molecule and cause transcription.
If the receptor R is actually on a free protein, and the molecule H (or X) binds to it to activate it, and then it goes and sits on the DNA somewhere to block mRNA transcription, then in this case it would down regulate mRNA transcription to have more H or X in the nucleus. It can happen either way, and combinations of both ways as well that change depending on their concentrations. For instance imagine a third protein P that bumps into H's and turns them into M's (an inactivated form of H). If protein P was only able to de-activate H and not X, then adding more X would not act like H in terms of activity or regulation because X's would not become M's, and M itself may trigger yet another protein that keeps track of how many M's there are and signals for more H's if all the M's disappear for a long period.