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Endocrine, paracrine and intracrine mechanisms of growth regulation in normal and malignant breast epithelium
Published in A. R. Genazzani, Hormone Replacement Therapy and Cancer, 2020
J. R. Pasqualini, G. S. Chetrite
Very little information is available on the regulation of estrogen sulfotransferase expression in breast cancer. Recent data have shown that in hormone-dependent breast cancer cells (MCF-7, T-47D), low concentrations (5 × 10–7 mol/l) of promegestone (R-5020) can increase the enzyme activity, while higher concentrations (5 × 10–5 mol/l) decrease this activity. This dual effect is correlated with the mRNA expression of estrogen sulfotransferase which is modulated by promegestone in a similar manner62. A stimulatory effect on sulfotransferase activity was also found at low concentrations (5 × 10–8 − 5 × 10–7 mol/l) with medrogestone, nomegestrol acetate or tibolone and its 3α- and 3ß-hydroxy metabolites, in MCF-7 and T-47D cells51,63 (Figure 4).
Defects in Coagulation Factors Leading to Recurrent Pregnancy Loss
Published in Howard J.A. Carp, Recurrent Pregnancy Loss, 2020
The hormones of pregnancy, estrogen, progesterone, and hCG all affect thrombosis. Estrogen may alter the concentrations of clotting factors to a prothrombotic profile, e.g., raising FVII [60] and plasminogen activator (PAI-1) [61] and reducing antithrombin III [61]. In mice, estrogen sulfotransferase (a cytosolic enzyme that catalyzes the sulfoconjugation of estrogens) has a critical role in modulating estrogen activity in the mouse placenta during mid-gestation [62]. Inactivation of estrogen sulfotransferase caused local and systemic estrogen excess and an increase in tissue factor, leading to placental thrombosis and fetal loss. In addition, estrogen can either stimulate or inhibit the production of IL-1 and TNF cytokines [63].
Molecular Mechanisms of Endocrine Disruption in Estrogen Dependent Processes
Published in Rajesh K. Naz, Endocrine Disruptors, 2004
Robert M. Bigsby, Minerva Mercado-Feliciano, Josephine Mubiru
While the action of endogenous estrogens is terminated primarily by hydroxylation, the resulting catechol estrogens (as well as the parent compounds) can be further methylated or conjugated with the hydrophilic groups glucuronide and sulfate (see review).184 The estrogen sulfotransferases are enzymes that add a sulfate group to estrogens, thus deactivating the original molecule. Xenoestrogens and many polyhalogenated aromatic hydrocarbons are also metabolized by estrogen sulfotrans-ferases. Of the three forms of sulfotransferases, estrogen sulfotransferase (SULT1E1) shows the greatest capacity to sulfate xenoestrogens such as DES, BPA, and non-ylphenol.200,201
Steroid sulfatase inhibitors: the current landscape
Published in Expert Opinion on Therapeutic Patents, 2021
Hanan S. Anbar, Zahraa Isa, Jana J. Elounais, Mariam A. Jameel, Joudi H. Zib, Aya M. Samer, Aya F. Jawad, Mohammed I. El-Gamal
In gynecological diseases, STS activity was found present and active although the mRNA and protein levels are usually present in low concentration[46]. STS may have an important role in epithelial ovarian cancer (EOC) as the progression of EOC is correlated to 17β-estradiol (E2). The majority of EOC patients are postmenopausal women where their ovarian production of estrogen is intermitted. As a result, estrogens are synthesized locally in cancer cell by sulfatase pathway, specifically STS that convert the inactive sulfated steroids to its active form [6,47]. Additionally, in a study involved four clinical cases of ovarian cell tumor, it was found that steroidogenic enzymes in tumor cells have moderate to strong expression. These enzymes include STS, estrogen sulfotransferase (EST), and aromatase (CYP19A1)[48].
Future directions in endometriosis treatment: discovery and development of novel inhibitors of estrogen biosynthesis
Published in Expert Opinion on Investigational Drugs, 2019
Fabio Barra, Andrea Romano, Giovanni Grandi, Fabio Facchinetti, Simone Ferrero
Another important source of estrone and estradiol is their conjugated forms via the STS activity that can be detected in the blood bathing the endometriotic implants. Sulpho-conjugated steroids possess higher water solubility, increased stability, and longer half-life than unconjugated compounds; despite not being able to directly bind to steroid-receptors, they serve as a reservoir for the formation of biologically active steroids. In contrast to STS, the enzyme estrone sulfotransferase (SULT1E1) antagonizes the action of STS by conjugating estrone with a sulfate moiety [11]. It has been suggested that in endometriotic tissue, the expression and activity of STS prevail over SULT1E1, complying with the global increased production of estradiol [16].