DEHYDROEPIANDROSTERONE SULFOTRANSFERASE IN THE DEVELOPING HUMAN FETUS- QUANTITATIVE BIOCHEMICAL AND IMMUNOLOGICAL CHARACTERIZATION OF THE HEPATIC, RENAL, AND ADRENAL ENZYMES

The sulfation of the adrenal steroid dehydroepiandrosterone (DHEA) is a critical step in the provision of substrates for estrogen biosynthes is by the placenta during pregnancy. This enzyme reaction is catalyzed by a cytosolic sulfotransferase (ST) found in many key body tissues, and we have examined the ontogeny and localization of expression of th is important enzyme in three tissues: the liver, adrenal, and kidney. Hepatic DHEA ST expression increased with advancing gestational age be fore reaching near-adult levels in the early postnatal period, suggest ing an increased requirement for this enzyme in the liver as developme nt progresses, whereas in the adrenal and kidney there was no obvious ontogenic pattern. The enzyme was expressed at a 5-fold higher level i n the adrenal than in the liver and some 40-fold higher than in the ki dney. Comparison of enzyme activity measurements and quantitation of t he expression of DHEA ST by immunodot blot analysis with an anti-DHEA ST antibody preparation demonstrated the fragility of the enzyme activ ity and suggested that immunoquantitation was a superior method for as sessment of levels of expression of this enzyme in widely different ti ssue sources. Examination of the localization of DHEA ST in these tiss ues by immunohistochemistry showed that in liver, DHEA ST was expresse d in embryonic hepatocytes and continued to be expressed in these cell s into adulthood, when there was some concentration of immunostaining around central veins. In the fetus, the adrenal enzyme was expressed i n the fetal zone, whereas in adult tissue, staining was localized prin cipally to the zona reticularis. Renal DHEA ST was present in the prox imal and distal tubules, loops of Henle, collecting ducts, and their p rogenitors, but was at no time expressed in the vascular glomerulus. I n light of the broad substrate specificity of this enzyme toward other steroids, in particular bile acids and cholesterol, the information p resented forms a strong basis for further studies into the role of DHE A ST in modulating the activity of a number of biologically active and potentially toxic steroids in the developing human.