title: Is expression of rat breast matrix components influenced by estrogen, progestins and tibolone?
abstract: OBJECTIVE
  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.
authors.affiliation: Discipline of Gynecology.
authors.forename: E P
authors.initials: EP
authors.lastname: Cunha
authors.forename: L M
authors.initials: LM
authors.lastname: Pompei
authors.forename: T R
authors.initials: TR
authors.lastname: Theodoro
authors.forename: M L
authors.initials: ML
authors.lastname: Steiner
authors.forename: V F
authors.initials: VF
authors.lastname: Silva
authors.forename: E R A
authors.initials: ER
authors.lastname: Silveira
authors.forename: A M A A
authors.initials: AM
authors.lastname: Mader
authors.forename: M A S
authors.initials: MA
authors.lastname: Pinhal
authors.forename: C E
authors.initials: CE
authors.lastname: Fernandes
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001940:Breast / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004338:Drug Combinations; D004394:Dydrogesterone / Q000008:administration & dosage / Q000494:pharmacology; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000494:pharmacology; D009640:Norethindrone / Q000008:administration & dosage / Q000494:pharmacology; D009652:Norpregnenes / Q000008:administration & dosage / Q000494:pharmacology*; D011372:Progestins / Q000008:administration & dosage / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D000099175:Heparanase
chemical_list: D015415:Biomarkers; D004338:Drug Combinations; D004394:Dydrogesterone; D004958:Estradiol; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D005966:Glucuronidase; D019812:Heparan Sulfate Proteoglycans; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D017258:Medroxyprogesterone Acetate; D009640:Norethindrone; D009652:Norpregnenes; D011372:Progestins; D018809:Proliferating Cell Nuclear Antigen; D000099175:Heparanase; C418365:estradiol, norethindrone drug combination; C071927:perlecan; C074283:estradiol 3-benzoate; C027385:tibolone
keywords: ESTROGEN; EXTRACELLULAR MATRIX; PERLECAN; PROGESTOGEN; PROLIFERATION; PROTEOGLYCANS