# In Grave’s Disease, hyperthyroidism is produced by an IgG that causes prolonged activation of the TSH receptors and results in excessive secretion of T3 and T4. Explain why the negative feedback mechanism does not work in this disease.

Biol 439
8/6/15
Due 8/12/15 in class.
Problem Set 2 [ – 2 pts/day late]
1. In Grave’s Disease, hyperthyroidism is produced by an IgG that causes prolonged activation of the TSH receptors and results in excessive secretion of T3 and T4. Explain why the negative feedback mechanism does not work in this disease. Reference an internet source (URL) or book (5 points).

2. Chromatographic assay reveals that the total amount of T3 in the blood is 10 μg. You find that the various bound forms of the hormone are:
T3(free) = 0.5%
T3 ~ albumin = 12 %
T3~TBG = 69 %
and T3~pro-albumin = 18.5 %
Target tissue: heart whose Bmax of T3 receptors = 76 fmol of T3 receptor/mg protein (1 fmol = 10-15 mol), where you have 100 μg protein (total protein of which T3 receptors makes only a tiny fraction) in your heart assay. MW = 68 kDal = 68,000 g/mol [Dasmalopatra et al., Receptor, 2(4):213-223, 1992]. This reference is only for the MW of T3 receptor, and not for the solution to this question. Note: You won’t need the MW of T3 because you already have the amount in g.
This is another intuition question, a conceptual question. So, don’t get all caught up in equations. If you had freshman chemistry or physics, then you can solve the following:
Calculate the amount (in g) of available T3 and its receptor (also in g). How do the 2 amounts compare? Will Bmax be reached (10 points)?

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