Aromatase, inhibition

Anastrazole is a nonsteroidal, type H, aromatase inhibitor that is 200 times more potent than aminoglutethimide. It is eliminated primarily via hqDatic metabolism, has a terminal half life of 50 h with steady state concentrations achieved approximately 10 days with once daily dosing regimens. It is administered orally at a dose of 1 mg/day that achieves near maximal aromatase inhibition and hence estrogen suppression in breast cancer patients. No effect on adrenal steroidogenesis has been observed at up to ten times the daily recommended dose. When used in the metastatic setting, anastrozole has been shown... 

Dowsett M (1996) Biological background to aromatase inhibition. Breast 5 196-201... 

Tributyltin is well established as an aromatase inhibitor, and dibutyltin appears to have some potency also (exact characterization of the endocrine disrupting capacity of dibutyltin alone is difficult because of the presence of tributyltin as an impurity). Monobutyltin and mono- and dioctyltins have no aromatase inhibiting capacity in in vitro tests. No data are available for this end-point for the methyltins. 

In recent in vitro studies, an aromatase inhibiting effect on human placental microsomal extracts has been demonstrated with both tributyltin chloride and dibutyltin dichloride (Heidrich et al, 2001 Cooke,... 

Investigations of the aromatase inhibiting effects in in vitro assays gave no indicahon of an endocrine response after incubation with mono-, di-, or trioctyltin (Cooke, 2002). 

Monobutyltin No data available No. NOAELs >400-2000 mg/kg body weight per day (as MBTC) No aromatase inhibition in vitro No data available... 

Dibutyltin No significant neurotoxicity reported Yes. NOAEL = 2.5 (teratogenicity) and 1.0/5.0 (maternal toxicity) mg/kg body weight per day (as DBTC) Aromatase inhibition present (at least 10 times less potent than tributyltin) no imposex in vivo in invertebrates Yes. NOAEL could not be determined lowest dose reported to cause immunological effects = 2.5 mg/kg body weight per day (as DBTC)... 

Monooctyltin No neurotoxicity reported in 90-day studies Teratogenicity appears to be low (NOAEL = 120 mg/kg body weight per day) based on one study on a monooctyltin/dioctyltin mixture at 67 33 No aromatase inhibition in vitro NOAEL = 0.87 (decreased thymus weight) mg/kg body weight per day (as MOTC/DOTC mixture 65 35 )... 

Anxiolytic agents, pyrido[l,2-a]benzimida-zoles as, 36 (1999) 169 Aromatase inhibition and breast cancer, 26 (1989) 253 33 (1996) 147 Arthritis neurokinin receptors in, 43 (2005) 53... 

Chlebowski RT, Col N, Winer EP et al. (2002) American Society of Clinical Oncology Technology assessment of pharmacologic interventions for breast cancer risk reduction including tamoxifen, raloxifene, and aromatase inhibition. J Clin Oncol 20(15) 3328—3343... 

Ibrahim, A.R. and Abdul-Hajj, Y.J., Aromatase inhibition by flavonoids, J. Steroid Biochem. Mol. Biol, 37, 257, 1990. 

In healthy men, chronic melatonin administration (> 6 months) decreased sperm quality, possibly by aromatase inhibition in the testes. Until more is known, melatonin should not be used by couples who are actively trying to conceive. 

Out of a series of 42 compounds isolated and characterized in our investigation on B. papyrifera [41], comprising benzofurans, coumarins, and various types of flavonoids (biphenylpropanes, chalcones, flavans, flavanones, and flavones), only certain representatives of the latter class of compounds showed potent aromatase inhibition activity (Table 2). Flavanone 39 (2S)-2, 4 -dihydroxy-2"-(l -hydroxy- 1-methylethyl)-... 

The conversion of androstenedione to estrone is catalyzed by aromatase. Inhibition of aromatase (human estrogen synthetase) by several naturally occurring flavonoids, including quercetin, chrysin, and apigenin, has been described. The synthetic flavone 7,8-benzoflavone was most active. Aromatization of androstenedione was affected by several flavonoids, of which 7-hydroxy-flavone and 7,4-dihydroxyflavone were the most potent. 

For molluscs, there is also compelling international evidence of triorganotins having caused imposex and consequential population declines, in this case probably through metabolic endocrine disruption via aromatase inhibition or other androgenic mechanisms (Schulte-Oehlmann et al. 2000 Matthiessen 2003 Duft et al. 2005 Oehlmann et al. 2007). 

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