Sensitivity -vs- Responsiveness

[icepik]

The graph represents the plasma level of ACTH and Cortisol, over a 12-month duration, post-corticotropin therapy. What do you think the graph tells us us about the adrenocortical sensitivity and responsiveness to corticotropin.

 

 

I came across this question, and I was unsure about the context of "responsiveness" and "sensitivity" as it relates to hormones and physiology in general. I'm hoping someone out there has experience with using these two terms, in regards to this scenario.

 

 

This question is not about the mechanisms of negative feedback. It is solely to explain the difference between response and sensitivity using the graph. What does this graph tell you about the responsiveness and sensitivity of the adrenocortical?

 

My explanation:

 

Maximal responsiveness - maximal effect of a hormone on target cells.

Sensitivity - concentration of hormone at which half maximal response is seen.

 

"Response" in this example can be defined as : the TIME taken for the both glands to return to producing normal levels of hormones, after

 

1. Adrenocortical Sensitivity: Adrenocotical takes 12 months to produce a normal amount of cortisol. ACTH takes about 3 months to produce a normal amount of cortisol. However, it increases above and beyond that amount, and takes 12 months to return to normal producing capabilities. Therefore both of them takes the equal amount of time to reach normal levels, and both of them can be considered to have the same sensitivity to corticotropin.

 

2. Adrencortical responsiveness: Relatively small responsiveness to corticotropin compared to pituitary. The plasma concentration of cortisol, i.e. the response of the adrenocortical (to chronic absence of corticotropin) is much smaller than the ACTH concentration (the response of the pituitary). Furthermore, ACTH concentration increases over the normal plasma concentration suggesting a much higher responsiveness by the pituitary.

 

Note: my definition for "response" changes when I described adrenocortical responsiveness. I have no clue how to apply these simple principles, and I hope someone can enlighten me.

 

Thanks,

IP!

 

 

[Ringer]

I'm not knowledgeable of the relationship between ACTH and cortisol but it looks like a simple does response curve of cortisol regulation of ACTH. So sensitivity may by indicating the plasma concentration of ACTH needed to create a response of cortisol(or the amount of cortisol necessary to regulate ACTH to normal levels depending on what the relationship between the two is). Responsiveness may be talking the concentration of ACTH in which there is an initial increase in cortisol levels and the concentration of ACTH where both cortisol levels and ACTH levels normalize.

 

I don't know if this helps because I'm not familiar with the metabolic pathways of those two hormones, but that's what it seems like to me when I look at the chart.

[icepik]

I did some more digging. You are right, that it's actually ACTH effect on Cortisol. I decided to post what I wrote up, in case anyone wants to take a look.

 

ACTH levels increase rapidly for the first couple months. No cortisol is being produced up until about the 5^th month. During this period, barely any cortisol is being produced, despite rising levels of ACTH. The adrenocortical is basically absolutely “insensitive” to ACTH. Massive negative feedback from the exogenous hormones has probably down-regulated the number of ACTH receptors. Thus, the levels of ACTH were not enough to stimulate production of cortisol (high threshold). Therefore its sensitivity to ACTH is very, very low, post-steroidal therapy.

As the adrenocortical begins to recover from the massive negative feedback effect, and as ACTH production ramps up and beyond “normal” levels, the adrenocortical begins to produce cortisol. Sensitivity is still very low, but the seesaw effect between low sensitivity and high stimulus (levels of ACTH), is able to produce some cortisol. Therefore, we can say, the adrenocortical is still very low, but attainable. The high levels of ACTH, combined with the low levels of cortisol produced suggest the responsiveness of the adrenocortical is also very low.

As the amount of ACTH increases, and as the adrenocortical further recovers, both the sensitivity and responsiveness increases. The rising slope of the cortisol line gives a primitive interpretation /indication of the rising responsiveness. At the end of the 10^th month, ACTH production begins to decrease, but cortisol levels stay the same. We can assume that the adrenocortical has fully recovered from negative feedback, and has reached its “normal” state. The subsequent plateau of the cortisol line suggests that the “normal” responsiveness of the adrenocortical has been achieved. The responsiveness of the adrenocortical to ACTH after month 10 has not changed and thus this measurement can be considered its maximal responsiveness. The decrease in ACTH at the end is very important. It shows us that the sensitivity of cortisol has drastically changed. The same level of ACTH that produced a very,very low amount of of cortisol (shown at month 5), now produces a “normal” amount of cortisol shown at month 12, suggesting sensitivity has increased. Less ACTH is required to produce a response.

In summary, as the cortisol levels begin to increase, the sensitivity of the adrenocortical begins to increase. This is the minimum amount of ACTH to cause the adrenocortical to produce cortisol. Since the adrenocortical is recovering from negative feedback, its states are changing, and sensitivity is also changing/increasing. Responsiveness is best shown when the cortisol level plateaus. Despite rising ACTH levels, the cortisol is “capped” and this is the maximal responsiveness of the adrenocortical.