Effect of CGS 20267 on ovarian aromatase and gonadotropin levels in the rat
Abstract
Aromatase catalyzes the rate limiting step that converts androgens to estrogens. Postmenopausal women with hormone dependent breast cancer respond to first generation aromatase inhibitors such as aminoglutethimide with a marked suppression of circulating estradiol levels. In contrast, premenopausal women appear to be resistant to first generation aromatase inhibitors. The inability to block ovarian aromatase results from the low affinity of first generation inhibitors for the active site of the enzyme. Under these circumstances, the high substrate levels in the premenopausal ovary compete effectively with these inhibitors and do not allow binding of inhibitor to the active site of the enzyme. Second and third generation aromatase inhibitors with higher affinity for aromatase have now been developed and potentially could block ovarian aromatase. To test this possibility, we administered CGS 20267 (letrozole), a highly potent aromatase inhibitor, to cycling female rats. A dose dependent inhibition of uterine weight occurred with maximum effects produced by the 5 mg/kg/day dosage. During a period of 4 weeks, uterine weight was reduced to levels induced by ovariectomy. Ovarian tissue estradiol levels were inhibited by approximately...Continue Reading
References
Citations
Chemoprevention of LA7-Induced Mammary Tumor Growth by SM6Met, a Well-Characterized Cyclopia Extract
Related Concepts
Related Feeds
Breast Cancer: Chemo-Resistance
Some cancers are difficult to treat and aggressive including the "triple-negative" breast cancer. This type of cancer is chemoresistant even before chemotherapy begins. Here are the latest discoveries chemo-resistance in breast cancer.