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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aromatase is the rate limiting enzyme that catalyzes the conversion of androgens to estrogens. Blockade of this step allows treatment of diseases that are dependent upon estrogen. Over the past two decades, highly potent and specific aromatase inhibitors have been developed which block total body aromatization by over 99%. An important recent question is whether aromatase inhibitors are superior to the antiestrogens for treatment of hormone-dependent breast cancer. The third generation aromatase inhibitors have been compared to tamoxifen for the treatment of breast cancer in the advanced, adjuvant, and neoadjuvant settings. All of these studies suggest the superiority of aromatase inhibitors over tamoxifen. The mechanism responsible for the superiority of the aromatase inhibitors relates to the estrogen agonistic effects of tamoxifen. During exposure to estrogen deprived conditions and to tamoxifen, breast cancer cells adapt and upregulate the MAP kinase and PI-3 kinase pathways. These growth factor signaling pathways potentiate the estrogen agonistic properties of tamoxifen. Data from a large adjuvant therapy trial (ATAC trial) provide evidence that the aromatase inhibitors may also be superior for breast cancer prevention. The mechanism for superiority in this setting probably relates to the genotoxic effects of estradiol metabolites. The aromatase inhibitors may be also useful for the treatment of endometriosis and for ovulation induction as evidenced by preliminary data. The recent advances in development of the aromatase inhibitors clearly demonstrate the utility of these agents for treatment of breast cancer and potentially for other indications.
Steroids 2003 Sep
PMID:Inhibition of aromatase: insights from recent studies. 1295 61

Estrogen mediates biological effects on cell proliferation, differentiation, and homeostasis through estrogen receptor (ER). In addition to functioning as a ligand-activated nuclear transcription factor to directly regulate gene transcription, ER also mediates rapid activation of signaling pathways independent of its transcriptional activity. A subpopulation of ER localized to the cell membrane or cytoplasm has been proposed to mediate ER activation of signaling pathways. This review focuses on recent advances in our understanding of mechanisms responsible for ER cytoplasm/membrane localization, where rapid extra-nuclear signaling is initiated. These mechanisms include lipid modification of the receptor (palmitoylation) and interactions with membrane and cytoplasmic adaptor proteins including caveolins, striatin, p130Cas, Shc, HPIP, MTA-1s, and MNAR/PELP1. While it is clear that ER mediates rapid extra-nuclear signaling resulting in activation of signaling pathways such as Src/MAPK and PI-3 kinase/Akt, how ER extra-nuclear signaling influences overall ER/estrogen physiology is still not well understood. Future studies defining physiological roles of ER extra-nuclear actions and crosstalk with its nuclear counterparts will be important to our overall understanding of estrogen and ER biological functions.
Steroids 2011 Aug
PMID:Scaffolding proteins mediating membrane-initiated extra-nuclear actions of estrogen receptor. 2135 35