Decrease of the prostaglandin I2 binding capacity in thyroids from patients with Graves' disease.
Properties of prostaglandin (PG) I2-binding sites in human thyroids from euthyroid and thyrotoxic patients were investigated. The specific binding of 3H-iloprost (ZK 36374, a chemically stable PGI2-analogue) to normal thyroids approached saturation at a concentration of more than 150 nmoles/L and could be displaced most effectively by unlabeled iloprost (concentration causing the half maximal inhibition, IC-50 = 5.9 +/- 2.9 mumoles/L) and PGI2 (IC-50 = 9.8 +/- 3.1 mumoles/L) and less effectively by unlabeled PGF2 alpha (IC-50 = 847.9 +/- 123.8 mumoles/L) at 4 degrees C. The Scatchard analysis clearly indicated heterogeneity revealing the presence of 0.65 +/- 0.18 pmoles/mg protein at the high-affinity binding sites (equilibrium dissociation constant, Kd = 18.2 +/- 9.1 nmoles/L) and 5.35 +/- 1.6 pmoles/mg protein at the low-affinity binding sites (Kd = 151.3 +/- 43.1 nmoles/L). In contrast, in diffuse colloid struma derived from patients with Graves' disease a single class of binding sites with an apparent binding capacity of 0.18 +/- 0.05 pmoles/mg protein (Kd = 70.4 +/- 27.3 nmoles/L) was indicated. However, in diffuse colloid struma derived from euthyroid patients no difference in the number of binding sites and binding affinity of 3H-iloprost was noted compared to normal thyroids. The data provide evidence for the presence of specific PGI2-binding sites in the human thyroid gland and demonstrate a significant decrease of the receptor density in patients with Graves' disease. It is suggested, that PGI2 has an important role in the regulation of human thyroid function.
Virgolini
I
I
2nd Department of Nuclear Medicine, University of Vienna, Austria.
Hermann
M
M
Sinzinger
H
H
D001665:Binding Sites; D001667:Binding, Competitive; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D006111:Graves Disease / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D011485:Protein Binding; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D013696:Temperature; D013961:Thyroid Gland / Q000378:metabolism*; D013972:Thyrotropin / Q000097:blood
D008565:Membrane Proteins; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D013972:Thyrotropin; D011464:Epoprostenol