Glutathione S-transferases and thiol concentrations in embryonic and earlyfetal tissues

BACKGROUND: Glutathione S-transferases (GSTs) are important in intracellula r binding and transport of numerous compounds, and play a central role in h uman detoxification processes. Human GSTs mainly consist of class Pi (GSTP) , Mu (GSTM), Alpha (GSTA) and Theta (GSTT) enzymes, each subdivided into on e or more isoenzymes. They catalyse the conjugation of glutathione (GSH) to toxic compounds, resulting in more water-soluble and less biologically act ive products that may be easily excreted. The reactive -SH group in GSH is provided by cysteine, an important amino acid in GSH synthesis. METHODS: GS T expression, enzyme activity and concentrations of cysteine and GSH in cyt osolic fractions of organs from an embryo and a fetus at 8 and 13 weeks ges tational age respectively were investigated. RESULTS: GSTP(1) was predomina ntly present in all tissues of both the embryo and fetus. GSTA (GSTA(1) + G STA(2)) concentrations were moderate as compared with GSTP(1), whereas GSTM (1) was present in only low amounts. GSTT(1) was not detected in any tissue . GST activity was highest in organs exposed directly to amniotic fluid. In all embryonic and fetal organs, considerable amounts of GSH and cysteine w ere detected, with higher GSH concentrations in organs where lower cysteine concentrations were demonstrated. CONCLUSIONS: These results suggest that in embryonic and early fetal development cysteine, GSH and GSTs are present in high amounts, and that GSTP(1) is the most important GST isoform at the se developmental stages.