Sulfation of drugs and hormones in mid-gestation human fetus.

Background: Sulfotransferase is an important enzyme family that catalyses the transfer of a sulfate group from a donor substrate, 3'-phosphoadenosine-5'-phosphosulphate (PAPS), to an acceptor substrate which may be a drug, a hormone or a neurotransmitter that possesses a hydroxy or an amine group. Drugs and hormones are sulfated in human fetal tissues but a review on this topic has not yet been published.

Aims: The aim of this article is to review the literature on the sulfation of drugs and hormones in human fetus and, when possible, to compare the rate of sulfation in fetal and adult human tissues.

Study Design: A medline search was performed by using the following key words: "fetal sulfotransferase" and "sulfotransferase in fetus" with the limit of "human". The literature was collected, critically read and a written note was produced.

Subjects: The majority of studies were conducted with mid-gestation human fetuses and limited studies include younger and older fetuses.

Results: The sulfation rate of dopamine (SULT1A3) was 3-fold higher in fetal than adult liver whereas the sulfation rate of 4-nitrophenol (SULT1A1) was one order of magnitude lower in fetal than adult liver. Ritodrine is sulfated at a higher rate in the fetal than adult liver. The sulfation rates of dopamine, 4-nitrophenol and ritodrine varied considerably in the fetal liver and did not correlate with the gestation age. 3,3'-T2 was sulfated in human placenta and the sulfation rate of 3,3'-T2 correlated with SULT1A1 activity. Dehydroepiandrosterone sulfotransferase activity is 6-fold higher in the fetal than adult adrenal.

Discussion: Sulfotransferase activity develops early in the human fetal liver and is subjected to a remarkable interindividual variability. Because of this variability, the examined enzyme activities did not correlate with the gestation age. Hormones are extensively sulfated in human fetal liver and other tissues. Sulfated hormones may serve as circulating or intracellular stores from which the free hormone can be regenerated by the action of the sulfatases.