WILTIMS #106: Maximally confusing hormonal responses

TIL: Changing the number of hormone receptors on a membrane does not change the maximum response of the cell to hormonal stimulation, but it does change the sensitivity. If, however you change the affinity of the receptors to the hormone, then sensitivity remains constant as the maximum response changes. This is not the most intuitive concept, so here's an example to help explain it:

Say you have a membrane just filled to the brim with receptors. If you have another membrane with fewer receptors it will take more hormone for the second membrane to induce the same response. For either membrane, if you add infinite amounts of hormone you will still produce a maximal response, the second membrane just takes more hormone before it reaches that level (see graph 1 below). In other words, membrane #2 is less sensitive to the hormone.

If you instead have two membranes with the same number of receptors but one has a slightly defective version of the receptor*, that second membrane will not be able to reach the same maximum response as the first regardless of how much hormone you throw at it (graph #2 above). Membrane #2 is still equally sensitive to the hormone, it just can't do as much with the same signal. The new maximum rate will be reached just as fast and with the same amount of hormone, it will simply be lower. Thus the sensitivity has not changed, as represented by ED₅₀ above. ED₅₀ is shorthand for the effective dose to bind 50% of the membrane hormone receptors.

Still confused? Me too. If I find a better way to explain this, I'll come back to it... but don't hold your breath!

*This scenario also works if, instead of damaging the receptors, the number of receptors is reduced to a level so low that it cannot properly trigger the maximal cellular response.