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Sulfation of Thyroid Hormone and Dopamine during Human Development: Ontogeny of Phenol Sulfotransferases and Arylsulfatase in Liver, Lung, and Brain¹

Departments of Obstetrics and Gynecology (K.R., R.H., E.L.S.), Child Health (R.H.), and Molecular and Cellular Pathology (R.H., E.L.S., M.W.H.C.), University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, United Kingdom DD1 9SY; and Department of Internal Medicine, Erasmus University Medical School (E.K., T.J.V.), 3015 GD Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Dr. M. W. H. Coughtrie, Department of Molecular and Cellular Pathology, University of Dundee, Level 7, Ninewells Hospital, Dundee, Scotland, United Kingdom DD1 9SY. E-mail: m.w.h.coughtrie{at}dundee.ac.uk

Abstract

Sulfation is an important mechanism for regulating the biological activity of numerous hormones and neurotransmitters in man. Here we have investigated the ontogeny of sulfotransferases (SULT) and sulfatase (ARS) involved in the metabolism of thyroid hormone and dopamine. SULT1A1 enzyme activity was lower in postnatal liver and lung than in fetal tissues. Hepatic SULT1A3 (dopamine) was expressed at high levels early in development, but decreased substantially in late fetal/early neonatal liver and was essentially absent from the adult liver. In lung, significant SULT1A3 activity was observed in the fetus, but neonatal levels were considerably lower. In brain, the highest activity was observed in the choroid plexus for SULT1A1, with low and widespread activity for both SULT1A1 and SULT1A3 in other brain regions. SULT activity with 3,3'-diiodothyronine (3,3'-T₂) as substrate was measured in all tissues and correlated significantly with SULT1A1 activity (4-nitrophenol), suggesting that SULT1A1 is primarily responsible for the sulfation of this iodothyronine. The developmental expression of SULT1A3 and SULT1A1 in liver and brain was confirmed by immunoblot, and immunohistochemistry of developing liver showed substantial expression of these proteins in hemopoietic cells in fetal liver. We also detected low activity for the hydrolysis of 3,3'-T₂ sulfate by ARS, although there was less distinction between fetal and neonatal samples than with SULT activities. We have therefore shown that the developing fetus has substantial sulfation capacity. Sulfation may therefore play a major role in the homeostasis of hormones and other endogenous compounds as well as in detoxification in the fetus, particularly as other conjugating enzyme systems, such as the UDP-glucuronosyltransferases, are not expressed at significant levels until the neonatal period.

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