steriod binding proteins

[twesting2173]

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I'm sorry, I feel like such a leech. I just come on here to ask questions and everyone is really nice...but I don’t have anything to contribute. But I promise, as soon as this hell is over, I’ll figure out a way to contribute to these message boards. If nothing else, I’ll give away all of these ugly, ugly books that I cant wait to be done with.

So as mush as I love goljan, he has confused me. I thought I understand the concept of steroid binding proteins: if the binding protein concentration is up, then free level is down and there is less available for activity...right? So, for example, estrogen increases the syntheses of SHBG, so free levels of hormone goes down but total level of hormones stays the same.

But, as I understand goljan, he says (lec 33 36:00) that, indeed, estrogen will increae levels of binding globulins but T4 will stay the same. He says that the total will go up, but that the free level will same the same. I guess I could rationalize this and say that the free level is what is sensed and thus regulated...so feedback necessitates the increased production of hormone...so free levels will stay the same, but the total will increase (given the increase in binding globulin), but I don't think that this is correct. Maybe i'm not supposed to be thinking about estrogen and thyroid hormones together...eeek.

And then, in lec 28 (46:00), he talks about bi8nding globulin and copper in Wilson’s disease. I THINK he says that cirrhosis results after years of increased copper levels. He says that the decrease in liver activity lowers binding protein (ceruloplasmin), which increases free copper but decrease total copper. I don’t get it...why is different from the rationale he uses with sex hormones?

Freinds: don’t get this. I’m confused. This is probably easy, but I’m slow. Any help would really really be appreciated. Thanks again for all of your good notes and advice!

 

[stochastic]

So as mush as I love goljan, he has confused me. I thought I understand the concept of steroid binding proteins: if the binding protein concentration is up, then free level is down and there is less available for activity...right? So, for example, estrogen increases the syntheses of SHBG, so free levels of hormone goes down but total level of hormones stays the same.

But, as I understand goljan, he says (lec 33 36:00) that, indeed, estrogen will increae levels of binding globulins but T4 will stay the same. He says that the total will go up, but that the free level will same the same. I guess I could rationalize this and say that the free level is what is sensed and thus regulated...so feedback necessitates the increased production of hormone...so free levels will stay the same, but the total will increase (given the increase in binding globulin), but I don't think that this is correct. Maybe i'm not supposed to be thinking about estrogen and thyroid hormones together...eeek.

And then, in lec 28 (46:00), he talks about bi8nding globulin and copper in Wilson’s disease. I THINK he says that cirrhosis results after years of increased copper levels. He says that the decrease in liver activity lowers binding protein (ceruloplasmin), which increases free copper but decrease total copper. I don’t get it...why is different from the rationale he uses with sex hormones?

Freinds: don’t get this. I’m confused. This is probably easy, but I’m slow. Any help would really really be appreciated. Thanks again for all of your good notes and advice!

I believe SHBG has a higher affinity for T than E2. So, increased E2 increases SHBG synthesis. Increasing SHBG acts as an estrogen amplifier by reducing free testosterone levels more than it reduces free estrogen levels, thus giving a net estrogenic effect on the patient. There should be an increase in total hormone, both T and E2. The main point here should be the estrogen amplification effect of SHBG.

You are correct about TBG. Total amount goes up when TBG increases, but free amount stays the same.

Wilson's disease has increased copper absorption from small intestine, but decreased excretion by the liver in the form of ceruloplasmin. Total levels of copper are therefore lower, but the free levels are higher. It is the free copper that causes organ damage.

From what I can tell it is the same rationale for each situation. The more binding globulin, the higher the total concentration. The lower the binding globulin, the decreased total amount. In the case of SHBG, free levels of E2 and T remain relatively constant except there is always a relative free-E2 amplification over free-T. In the case of TBG, T4 is regulated by TSH and free levels remain constant. In the case of copper, Cu is being absorbed too quickly, but the marked decrease of ceruloplasmin decreases total Cu (nothing new here). Free levels go up because there is a pathological increased uptake and decreased excretion.