Estrogen synthesis from C19 precursors is catalyzed by aromatase cytochrome P450. Overexpression of aromatase through atypical promoter usage (use of promoter II) in adipose tissue contributes to breast cancer development and progression. One tumor-derived factor that appears to contribute to this process is prostaglandin E2 (PGE2). A factor that regulates aromatase expression downstream of PGE...

Studies have shown that female mosquitofish living downstream of a paper mill located on the Fenholloway River, Florida, have masculinized secondary sex characteristics, including altered anal fin development and reproductive behavior. Masculinization can be caused by exposure to androgens in the water or from an alteration in aromatase activity in the fish. We hypothesized that aromatase activ...

The local regulation of ovarian aromatase enzyme in polycystic ovary syndrome (PCOS) was studied with aromatase conversion and [11C]vorozole-binding assays to analyze aromatase activity, substrate-enzyme affinity and number of aromatase binding sites in non-cultured human granulosa cells (GC) incubated with different sources and preparations of follicular fluid (FF). Incubation with FF from wom...

Following their successful implementation for the treatment of metastatic breast cancer, the 'third-generation' aromatase inhibitors (anastrozole, letrozole, and exemestane) have now become standard adjuvant endocrine treatment for postmenopausal estrogen receptor-positive breast cancers. These drugs are characterized by potent aromatase inhibition, causing >98% inhibition of estrogen synthesis...

Transient postnatal hypothyroidism in male rats induces a prolonged proliferation of immature Sertoli cells. This change in Sertoli cell replication at young ages is coincident with enhanced and prolonged aromatase activity that leads to a marked increase in the conversion of androgens into estrogens. Both events are drastically inhibited by tri-iodothyronine (T(3)) replacement either in vivo o...

Aromatase is an enzyme that facilitates the conversion of androgens to estrogens and may play a role in mood and mental status. The main theme of this thesis is the imaging of brain aromatase by use of the PET technique. The PET tracer for aromatase, C-labeled vorozole (VOZ) was developed and evaluated by with in vitro and in vivo methods. In vitro experiments using rat brain showed that VOZ wa...

A major mechanism through which melatonin reduces the development of breast cancer is based on its anti-estrogenic actions by interfering at different levels with the estrogen-signalling pathways. Melatonin inhibits both aromatase activity and expression in vitro (MCF-7 cells) as well as in vivo, thus behaving as a selective estrogen enzyme modulator. The objective of this study was to study th...

The mammalian testis serves two main functions: production of spermatozoa and synthesis of steroids; among them estrogens are the end products obtained from the irreversible transformation of androgens by a microsomal enzymatic complex named aromatase. The aromatase is encoded by a single gene (cyp19) in humans which contains 18 exons, 9 of them being translated. In rats, the aromatase activity...

Stroke risk and outcome are strongly modified by estrogen. In addition to ovaries, estrogen is produced locally in peripheral tissue by the enzyme aromatase, and extragonadal synthesis becomes the major source of estrogen after menopause. Aromatase gene deletion in female mice exacerbates ischemic brain damage after stroke. However, it is not clear which cell type is responsible for this effect...

Estrogen signaling is critical in the progression of tumors that bear estrogen receptors. In most patients with breast cancer, inhibitors that block interactions of estrogen with its receptors or suppress the production of endogenous estrogens are important interventions in the clinic. Recent evidence now suggests that estrogen also contributes to the pathogenesis of non-small cell lung cancer ...