Sex-Dependent Role of Estrogen Sulfotransferase and Steroid Sulfatase in Metabolic Homeostasis

Abstract

Sulfonation and desulfation are two opposing processes that represent an important layer of regulation of estrogenic activity via ligand supplies. Enzymatic activities of families of enzymes, known as sulfotransferases and sulfatases, lead to structural and functional changes of the steroids, thyroids, xenobiotics, and neurotransmitters. Estrogen sulfotransferase (EST) and steroid sulfatase (STS) represent negative and positive regulation of the estrogen activity, respectively. This is because EST-mediated sulfation deactivates estrogens, whereas STS-mediated desulfation converts the inactive estrogen sulfates to active estrogens. In addition to the known functions of estrogens, EST and STS in reproductive processes, regulation of estrogens and other signal molecules especially at the local tissue levels has gained increased attention in the context of metabolic disease in recent years. EST expression is detectable in the subcutaneous adipose tissue in both obese women and men, and the expression of EST is markedly induced in the livers of rodent models of obesity and type 2 diabetes. STS was found to be upregulated in patients with chronic inflammatory liver diseases. Interestingly, the tissue distribution and the transcriptional regulation of EST and STS exhibit obvious sex and species specificity. EST ablation produces completely opposite metabolic phenotype in female and male obese mice. Adipogenesis is also differentially regulated by EST in murine and human adipocytes. This chapter focuses on the recent progress in our understanding of the expression and regulation EST and STS in the context of metabolic homeostasis.

Underestimated Aspect of Mucopolysaccharidosis Pathogenesis: Global Changes in Cellular Processes Revealed by Transcriptomic Studies

“…The steroid sulfatase is the STS gene product. This enzyme catalyzes the hydrolysis of various 3-beta-hydroxysteroid sulfates, which are precursors for crucial biologically active compounds such as estrogens, androgens, and cholesterol [36]. Expression of STS is considerably impaired in MPS IIID ( Figure 5).…”

Estrogen receptor signaling mechanisms

“…These compounds have gained significant attention due to their little estrogenic effects, antiproliferative properties, and ability to control estrogen synthesis (Purohit & Reed, 2002; Purohit et al, 2006). Moreover, catechol estrogens can also be conjugated by estrogen sulfotransferases and UDP-glucuronyltransferases (Cheng et al, 1998; Garbacz, Jiang, & Xie, 2017). In a conjugation reaction, hormones become water soluble and excreted from the body (Lakhani, Venitz, Figg, & Sparreboom, 2003).…”

Sex differences in metabolic regulation and diabetes susceptibility

“…In addition, it is also important to consider the regulation of local steroid activity resulting from sulfonation and desulfation processes, which lead to hormonally deactivated or activated molecules, respectively. In mouse models, both steroid sulfatase and oestrogen sulfotransferase (EST) have been demonstrated to interfere with the pathogenesis of type 2 diabetes in a sex-specific manner [56]. For instance, inactivation of EST, the enzyme responsible for oestrogen deactivation, increases energy expenditure, improves insulin sensitivity, and reduces hepatic gluconeogenesis and lipogenesis in different mouse models of obesity-related metabolic disorders, but only in females [57].…”