Explain why the negative feedback mechanism does not work | Homework Help

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.

2. Chromatographic assay reveals that the total amount of T₃ in the blood is 10 ?g.  You find that the various bound forms of the hormone are:

T_3(free) = 0.5%

T₃ ~ albumin = 12 %

T₃~TBG = 69 %

and T₃~pro-albumin = 18.5 %

Target tissue: heart whose B_max of T₃ receptors = 76 fmol of T₃ receptor/mg protein                    (1 fmol = 10^-15 mol), where you have 100 ?g 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 B_max be reached?