Biochemistry and reproductive endocrinology of estrogen sulfotransferase.
Estrogen sulfotransferase is a cytosolic enzyme that catalyzes the sulfoconjugation and inactivation of estrogens. Significant progress has been made in the last few years regarding the structure, substrate specificity, tissue expression, and regulation of mammalian estrogen sulfotransferases. The enzyme has high affinity for estrogens and is expressed in a number of estrogen target tissues, including the male and female reproductive systems. Expression of the enzyme in the testis has been particularly well characterized. In the testis, estrogen sulfotransferase is localized selectively to Leydig cells and its expression in these cells is dependent on LH and androgen. It was concluded, from both in vitro and in vivo studies, that estrogen sulfotransferase can function as an effective modulator of local estrogen activity in target tissues. The finding that certain hydroxylated polychlorinated biphenyls are potent inhibitors of the human estrogen sulfotransferase enzyme raises the possibility that environmental chemicals can cause endocrine disruption by enhancing endogenous estrogen activity through inhibition of steroid transformation enzymes such as estrogen sulfotransferase. This provides a new paradigm in explaining the endocrine disrupting potential of environmental chemicals that have low or no binding affinities for steroid hormone receptors.
Song
W C
WC
Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104 USA. Song@spirit.gcrc.upenn.edu
D000818:Animals; D004702:Endocrine Glands / Q000187:drug effects / Q000502:physiology*; D004785:Environmental Pollutants / Q000633:toxicity; D004967:Estrogens / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D012098:Reproduction / Q000187:drug effects / Q000502:physiology*; D015238:Sulfotransferases / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D014018:Tissue Distribution
D004785:Environmental Pollutants; D004967:Estrogens; D015238:Sulfotransferases; C020122:estrone sulfotransferase