Is expression of rat breast matrix components influenced by estrogen, progestins and tibolone?

• Published in: Climacteric : the journal of the International Menopause Society 2015-08, Vol.18 (4), p.523-527
• Main Authors: Cunha, E. P., Pompei, L. M., Theodoro, T. R., Steiner, M. L., Silva, V. F., Silveira, E. R. A., Mader, A. M. A. A., Pinhal, M. A. S., Fernandes, C. E.
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers - metabolism; Breast - drug effects; Breast - metabolism; Breast cancer; Cell growth; Cell Proliferation - drug effects; Drug Combinations; Dydrogesterone - administration & dosage; Dydrogesterone - pharmacology; Endocrine therapy; Estradiol - administration & dosage; Estradiol - analogs & derivatives; Estradiol - pharmacology; ESTROGEN; Estrogen Receptor Modulators - administration & dosage; Estrogen Receptor Modulators - pharmacology; Estrogens - administration & dosage; Estrogens - pharmacology; EXTRACELLULAR MATRIX; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Female; Glucuronidase - metabolism; Heparan Sulfate Proteoglycans - metabolism; Hormones; Immunohistochemistry; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Medroxyprogesterone Acetate - administration & dosage; Medroxyprogesterone Acetate - pharmacology; Norethindrone - administration & dosage; Norethindrone - pharmacology; Norpregnenes - administration & dosage; Norpregnenes - pharmacology; PERLECAN; Progestins - administration & dosage; Progestins - pharmacology; PROGESTOGEN; Proliferating Cell Nuclear Antigen - metabolism; PROLIFERATION; PROTEOGLYCANS; Random Allocation; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Side effects
• ISSN: 1369-7137; 1473-0804
• DOI: 10.3109/13697137.2015.1007122

Abstract Aim To study the effects of estrogen therapy, alone or combined with progestogens, and of tibolone on the expression of heparanase (HSPE), extracellular matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), perlecan and proliferating cell nuclear antigen (PCNA) in normal breast tissue. Methods Thirty 250-day-old Wistar rats were castrated and 3 weeks later received one of the following treatments by gavage for 5 weeks: (1) estradiol benzoate; (2) estradiol benzoate + medroxyprogesterone acetate; (3) estradiol benzoate + norethisterone acetate; (4) estradiol benzoate + dydrogesterone; (5) tibolone; (6) placebo. Following treatment, the expressions of mRNA for HSPE, MMP-2 and MMP-9 were analyzed by real-time PCR and the protein expressions of HSPE, MMP-2, MMP-9, perlecan and PCNA were quantified by immunohistochemistry. Results There was a statistically significant difference among the groups for the expression of HSPE mRNA due to high levels in the tibolone group. The groups differed in terms of PCNA, with lower levels found in the tibolone group followed by the estradiol benzoate + dydrogesterone group. A statistically significant positive correlation was observed for PCNA versus perlecan and MMP-9. Conclusions There was no difference in the effects of combinations of estradiol and different progestogens on extracellular matrix components, and breast cell proliferation was associated with increases in perlecan and MMP-9.