Regulation of Aromatase Expression by Hormones, Drugs, Pesticides and Environmental Pollutants in Canine Mammary CMT-U27 Cells
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1
University of Thessaly, Laboratory of Pharmacology and Toxicology, Greece
Introduction. Aromatase is a member of the P450 family (CYP19, cytochrome P450arom) and is the enzyme responsible for the conversion of testosterone to 17β-estradiol. P450arom is present in many tissues, including the gonads, brain, placenta, bone and adipose tissue. Aromatase expression is affected by a wide range of agents, such as steroid hormones, drugs, pesticides and environmental pollutants. In the present study, we investigate the effect of a wide variety of agents (including hormones, drugs, pesticides and antioxidants) on aromatase expression in the canine mammary CMT-U27 cell line. Aromatase expression was assessed using quantitative real-time PCR.
Materials and Methods. Canine mammary tumor CMT-U27 cells were grown in RPMI 1640 medium containing 10% Fetal Calf Serum and 1% Antibiotic-antimycotic, and incubated in 5% CO2 for 24 hours at 37º C. Total RNA was extracted from the cells using Trizol LS. Synthesis of cDNA was performed using M-MLV reverse transcriptase. Quantitative real-time PCR was performed on a Roche LightCycler 2.0 system using KAPA SYBR Fast qPCR Kit.
Results. Progesterone, estradiol, corticosterone, rapamycin, metformin, DFU, UDP4, UDP7, T3, prochloraz, DCA, rhapontin, genistein, bisphenol A, and epigallochetin gallate (EGCG) inhibited the expression of aromatase (p<0.05). BuNa, rosiglitazone, vitamin D3, curcumin, H-89 and roscovitine also inhibited aromatase expression, but the results were not statistically significant (p>0.05). Dexamethasone, propamocarb, forskolin, atrazine, quercetin, TTNPB, fenofibrate, and retinoic acid induced aromatase expression. (p<0.05)
Conclusion. The results suggest that aromatase expression is regulated by a number of chemically and mechanistically diverse agents, and further investigation is needed to further clarify the role of these agents in aromatase activity.
Keywords:
Aromatase,
P450 cytochrome,
drugs
Conference:
8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010, Thessaloniki, Greece, 1 Oct - 5 Oct, 2010.
Presentation Type:
Poster
Topic:
Xenobiotics and reproduction
Citation:
Mavridis
SK and
Pappas
AS
(2010). Regulation of Aromatase Expression by Hormones, Drugs, Pesticides and Environmental Pollutants in Canine Mammary CMT-U27 Cells.
Front. Pharmacol.
Conference Abstract:
8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010.
doi: 10.3389/conf.fphar.2010.60.00162
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Received:
05 Mar 2011;
Published Online:
04 Nov 2010.
*
Correspondence:
Dr. Savvas K Mavridis, University of Thessaly, Laboratory of Pharmacology and Toxicology, Thessaly, Greece, smavrid@vet.uth.gr