This project investigates basic mechanisms involved in steroid synthesis, modification and action. We are currently focusing on the expression, function, and regulation of steroid sulfoconjugating enzymes that comprise the family of steroid sulfotransferases. To date, we have purified, sequenced and cloned an estrogen sulfotransferase (EST) and two 3-hydroxysteroid sulfotransferases (HST). The EST gene has been cloned and its transcriptional regulation and tissue expression are being analyzed. The EST gene was found to contain steroid response elements in its 5'-flanking region and to be regulated by glucocorticoids and estrogens. We have also isolated HSTs that exhibit stereospecificity for the 3-hydroxyl group: one HST (32 kDa) acts only on the 3alpha- hydroxyl group and the other (33 kDa) acts only on the 3beta-hydroxyl group of the steroid molecule. EST and 3alpha/beta HST are differentially expressed in the mammalian adrenal cortex. In addition, whereas EST is localized to the nucleus, as well as extranuclear sites, the HSTs are found only in the cytoplasmic compartment. The high concentration of EST in nuclei, and the finding that the level of EST can be increased by ACTH, strongly suggest that EST plays a role in modulating the ability of estrogens to regulate gene expression in ACTH-responsive adrenocortical cells.
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