Steroid sulfotransferases.

Human dehydroepiandrosterone sulfotransferase (DHEA-ST) catalyzes the sulfonation of DHEA, cholesterol, pregnenolone as well as androsterone. RNA blot analysis shows two DHEA-ST mRNA species of 1.3 and 1.8 kb that are expressed similarly in liver and adrenals. To determine whether the form expressed in adrenals is distinct or identical with the one expressed in liver, we have cloned and sequenced the 1.8 kb DHEA-ST cDNA from human adrenal cDNA library. Except for one nucleotide difference, the human adrenal and liver DHEA-ST cDNAs are identical. Using expression vectors containing the chloramphenicol acetyltransferase (CAT) reporter gene ligated to various fragments of the DHEA-ST gene promoter, we have shown that DHEA-ST gene promoter activity is stimulated by estradiol (E2). The E2 stimulation is inhibited by the anti-estrogen EM-139. In contrast to human DHEA-ST, guinea pig hydroxysteroid sulfotransferases show high substrate- and stereo-selectivity. We have cloned a chiral-specific pregnenolone sulfotransferase (PREG-ST) which catalyzes mainly the transformation of pregnenolone to pregnenolone sulfate. Estrogen sulfotransferase catalyzes the conversion of estrone and estradiol to their inactive sulfated forms and could thus play a major role in the control of estrogen levels in target tissues. Recently, using a probe derived from bovine estrogen sulfotransferase, we have cloned a cDNA and gene that we first named human estrogen sulfotransferase (hEST) since the expressed enzyme is able to transform estrone to estrone sulfate. Actually, the Hugo nomenclature committee named this gene STM gene because it also codes for monoamine-sulfating phenol-sulfotransferase (M-PST). hEST1 possesses the same coding and 3'-untranslated region as human brain aryl sulfotransferase (HAST) and M-PST, but different 5'-noncoding region. Analysis of hEST1 gene sequence indicates that hEST1 and HAST3 or M-PST mRNA species are transcribed from a single hEST1 gene by alternative promoters using two separate exon 1, named exon Ia and exon Ib. We also described the identification of a third mRNA species (M-PST gamma) issued from the STM gene and the characterization of the structure of the phenol-sulfating phenolsulfotransferase (STP) gene that is highly homologous to the STM gene. Similar to STM, the STP gene generates multiple mRNA species that differ only in the 5'-untranslated sequence.