Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibition of estrogen production provides effective therapy for patients with hormone-dependent breast cancer. The source of estrogens in premenopausal women is predominantly the ovary, but after the menopause, estradiol is synthesized in peripheral tissues through the aromatization of androgens to estrogens. Uptake from plasma is the primary mechanism for maintenance of estradiol concentrations in breast cancer tissue in premenopausal women, whereas several steps may be operant in postmenopausal women. These include enzymatic synthesis of estradiol via sulfatase, aromatase, and 17 beta-hydroxysteroid dehydrogenase in the tumor itself. Aromatization of androgens secreted by the adrenal to estrogens in peripheral tissues and transport to the tumor via circulation in the plasma provides another means of maintaining breast tumor estradiol levels in postmenopausal women. These various sources contribute to the high tissue estrogen levels measured in breast tumor tissue. To effectively suppress tissue concentrations of estrogens and circulating estradiol in postmenopausal patients, various aromatase inhibitors have been developed recently. These include steroidal inhibitors such as 4-hydroxy-androstenedione as well as non-steroidal compounds with imidazole and triazole structures. The most potent of these, CGS 20267, is reported to suppress levels of active estrogens (i.e., estrone, estrone sulfatase, and estradiol) by more than 95%. This compound can suppress both serum and 24-hr urine estrogens to a greater extent than produced by the second generation inhibitor, CGS 16949A. CGS 20267 is highly specific since it does not affect cortisol and aldosterone serum levels during ACTH stimulation tests nor sodium and potassium balance in 24-hr urine samples.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aromatase inhibitor development for treatment of breast cancer. 774 29

Ovine parturition is initiated by increases in fetal hypothalamus-pituitary-adrenal (HPA) axis activity, which in turn increase placental estrogen biosynthesis and ultimately increase uterine contractility. In addition to the action in the uterus, estrogens augment fetal ACTH secretion. In late gestation, estrone sulfate is more abundant in fetal plasma than is unconjugated estrone. We studied hypothalamus, hippocampus, and brain stem tissue from fetal, neonatal, and adult sheep to test the hypothesis that the ovine brain contains estrogen sulfatase activity. We found that the activity in the hippocampus was significantly increased in late-gestation fetuses compared with both younger and older animals. No significant change in either hypothalamus or brain stem was revealed; however, the activity in all brain areas was high. Immunohistochemistry revealed the presence of estrogen sulfatase in the paraventricular nucleus of the hypothalamus, the nucleus of the solitary tract, and the rostral ventrolateral medulla. We conclude that ovine fetal hypothalamus, hippocampus, and brain stem contain estrogen sulfatase activity and that the activity in the hippocampus is developmentally regulated.
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PMID:Ontogeny of estrogen sulfatase activity in ovine fetal hypothalamus, hippocampus, and brain stem. 1036 43

Low endogenous levels of dehydroepiandrosterone (DHEA) and/or its sulfoconjugated derivative DHEA-S have been associated with diseases such as lupus, cancer, and diabetes. Circulating concentrations of DHEA and DHEA-S resulting from endogenous production or hormone supplementation may also be relevant in psychiatric illness. Drugs may significantly increase or decrease circulating concentrations of these adrenal androgens by various mechanisms. Some agents, such as dexamethasone, affect the HPA axis by inhibiting ACTH and therefore decrease DHEA and DHEA-S concentrations. Central nervous system agents, including carbamazepine and phenytoin, induce the P450 enzymes that metabolize DHEA and DHEA-S and therefore decrease circulating concentrations of these hormones. Danazol alters the ratio between DHEA and DHEA-S by inhibiting sulfatase. As research moves forward to better understand the relationships of these adrenal androgens with health and disease, it is essential that studies be designed to control for the influence of administered pharmaceuticals on DHEA and DHEA-S.
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PMID:The influence of hormones and pharmaceutical agents on DHEA and DHEA-S concentrations: a review of clinical studies. 1186 61