Human thyroid phenol sulfotransferase enzymes 1A1 and 1A3: activities in normal and diseased thyroid glands, and inhibition by thyroid hormones and phytoestrogens.
Sulfation by sulfotransferase enzymes (SULTs) is an important pathway for the metabolism of thyroid hormones and phytoestrogens. Intrathyroidal SULTs may contribute to the processing of thyroid hormones for the reutilization of iodide. SULT1A1 and SULT1A3 activities were identified in normal and diseased human thyroid glands. Biochemical properties that included apparent K(m) values, thermal stabilities, and responses to inhibitors were characterized in a normal human thyroid high speed supernatant pool. Apparent K(m) values for SULT1A1 and SULT1A3 activities with the model substrates p-nitrophenol and dopamine were 0.58 +/- 0.04 and 11.3 +/- 1.3 microm, respectively. Activities of SULT1A1 and SULT1A3 determined in individual normal thyroid (n = 35), nodular goiter (n = 26), and autoimmune thyroid disease (n = 25) glands were 0.34 +/- 0.06, 0.52 +/- 0.09, and 0.82 +/- 0.19 U/mg protein for SULT1A1, respectively, and 0.22 +/- 0.04, 0.21 +/- 0.04, and 0.48 +/- 0.11 U/mg protein for SULT1A3, respectively. Both SULT activities in autoimmune thyroid disease glands were significantly higher than those in normal thyroids. Only 3,3'-diiodothyronine (3,3'-T(2)) and the phytoestrogen daidzein served as substrates for the normal thyroid SULT activities, yet each thyroid hormone and phytoestrogen tested were found to inhibit thyroid SULT1A1 and SULT1A3 activities. The preference of thyroid gland SULT activities for 3,3'-T(2) suggests that sulfation may enhance degradation of intrathyroidal 3,3'-T(2) for iodide reutilization. Inhibition of these SULT activities by the exogenous phytoestrogens daidzein and genistein, with a potential decrease in iodide reutilization, presents another mechanism through which these compounds may adversely affect human thyroid function.
Ebmeier
Christopher C
CC
Section of Endocrinology, Veterans Affairs Medical Center, Creighton University Medical Center,4101 Woolworth Avenue, Omaha, Nebraska 68105, USA.
Anderson
Robert J
RJ
D015239:Arylsulfotransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D048789:Phytoestrogens / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012965:Sodium Chloride / Q000494:pharmacology; D015238:Sulfotransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013696:Temperature; D013959:Thyroid Diseases / Q000201:enzymology*; D013961:Thyroid Gland / Q000201:enzymology*; D013963:Thyroid Hormones / Q000494:pharmacology*
D048789:Phytoestrogens; D013963:Thyroid Hormones; D012965:Sodium Chloride; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; C403170:monoamine-sulfating phenol sulfotransferase