Estrogen sulfotransferase inhibits adipocyte differentiation

Mol Endocrinol. 2011 Sep;25(9):1612-23. doi: 10.1210/me.2011-1089. Epub 2011 Aug 4.


The estrogen sulfotransferase (EST) is a phase II drug-metabolizing enzyme known to catalyze the sulfoconjugation of estrogens. EST is highly expressed in the white adipose tissue of male mice, but the role of EST in the development and function of adipocytes remains largely unknown. In this report, we showed that EST played an important role in adipocyte differentiation. EST was highly expressed in 3T3-L1 preadipocytes and primary mouse preadipocytes. The expression of EST was dramatically reduced in differentiated 3T3-L1 cells and mature primary adipocytes. Overexpression of EST in 3T3-L1 cells prevented adipocyte differentiation. In contrast, preadipocytes isolated from EST knockout (EST-/-) mice exhibited enhanced differentiation. The inhibitory effect of EST on adipogenesis likely resulted from the sustained activation of ERK1/2 MAPK and inhibition of insulin signaling, leading to a failure of switch from clonal expansion to differentiation. The enzymatic activity of EST was required for the inhibitory effect of EST on adipogenesis, because an enzyme-dead EST mutant failed to inhibit adipocyte differentiation. In vivo, overexpression of EST in the adipose tissue of female transgenic mice resulted in smaller adipocyte size. Taken together, our results suggest that EST functions as a negative regulator of adipogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology*
  • Adipocytes / drug effects
  • Adipocytes / enzymology*
  • Adipogenesis / drug effects
  • Adipogenesis / genetics
  • Adipose Tissue / drug effects
  • Adipose Tissue / enzymology
  • Animals
  • Cell Differentiation* / drug effects
  • Cell Differentiation* / genetics
  • Cell Size / drug effects
  • Enzyme Activation / drug effects
  • Estradiol / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Gene Deletion
  • Gene Expression Regulation, Enzymologic / drug effects
  • Insulin / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • PPAR gamma / agonists
  • PPAR gamma / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Sulfotransferases / genetics
  • Sulfotransferases / metabolism*


  • Insulin
  • PPAR gamma
  • RNA, Messenger
  • Estradiol
  • Extracellular Signal-Regulated MAP Kinases
  • Sulfotransferases
  • estrone sulfotransferase