OBJECTIVE Reported associations between endogenous steroid hormone levels and cardiovascular disease in the older population have been contradictory. We evaluated plasma steroid concentrations in terms of the dimensions of the common carotid artery wall layers as a measure of the extent of atherosclerosis. METHODS A subgroup of 70-year-old participants (32 women and 50 men) from the Prospecti...

The crystal structures of human placental aromatase in complex with the substrate androstenedione and exemestane have revealed an androgen-specific active site and the structural basis for higher order organization. However, X-ray structures do not provide accounts of movements due to short-range fluctuations, ligand binding and protein-protein association. In this work, we conduct normal mode ...

Concurrent inhibition of aromatase and steroid sulfatase (STS) may provide a more effective treatment for hormone-dependent breast cancer than monotherapy against individual enzymes, and several dual aromatase-sulfatase inhibitors (DASIs) have been reported. Three aromatase inhibitors with sub-nanomolar potency, better than the benchmark agent letrozole, were designed. To further explore the DA...

Sex steroid action is critical to form sexually dimorphic nuclei, although it is not fully understood. We previously reported that masculinization of the principal nucleus of the bed nucleus of the stria terminalis (BNSTp), which is larger and has more neurons in males than in females, involves aromatized testosterone that acts via estrogen receptor-α (ERα), but not estrogen receptor-β (ERβ). H...

Use of steroid biosynthesis inhibitors to suppress estrogen production is a logical strategy in the treatment of women with hormone-dependent breast cancer. The clinical availability of aminoglutethimide as an inhibitor of cytochrome P-450-mediated steroid hydroxylations prompted study of the precise pharmacological and biochemical effects of this drug. Pharmacokinetic studies revealed that ami...

Inhibitors of steroid sulfatase are being developed as a novel therapy for hormone-dependent breast cancer in postmenopausal women. Data suggest that steroid sulfatase (STS) activity is much higher than aromatase activity in breast tumors and high levels of STS mRNA expression in tumors are associated with a poor prognosis. STS hydrolyzes steroid sulfates, such as estrone sulfate and dehydroepi...

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Aromatase is a key enzyme in intratumoral estrogen production required for the production of estrogens through the conversion of serum androgens in postmenopausal breast cancer patients. There have been, however, controversies regarding the intratumoral localization of aromatase in human breast carcinoma tissues. Therefore, we have first examined the intratumoral localization of aromatase mRNA/...

Cytochrome P450 aromatase (CYP19) plays an important role in steroid homoeostasis by converting androgens to estrogens. To evaluate the effects of benzo(a)pyrene (BaP), a model carcinogenic PAH and AhR ligand, on aromatase mRNA expression and enzyme activity, adult Fundulus were exposed to water-borne BaP (1 and 10 microg/L) for 15 days, and embryos were exposed to 10 microg/L for 10 days. Effe...

Castrated male quail display intense male-typical copulatory behavior in response to exogenous testosterone but ovariectomized females do not. The behavior of males is largely mediated by the central aromatization of testosterone into estradiol. The lack of behavioral response in females could result from a lower rate of aromatization. This is probably not the case because although the enzymati...