title: The effects of progesterone on matrix metalloproteinases in cultured human gingival fibroblasts.
abstract: BACKGROUND
  Although pregnancy gingivitis is widely believed to result from elevated hormone concentrations, the mechanism(s) involved in the etiology of this condition remain unknown. Paradoxically, despite the apparent inflammation for a prolonged period, pregnancy gingivitis rarely progresses to periodontitis and usually resolves postpartum. We used several methods to test in vitro the hypothesis that the elevated progesterone levels of pregnancy might inhibit the production of some of the matrix metalloproteinases (MMPs) that are responsible for periodontal destruction.
  
  
  METHODS
  Cultured human gingival fibroblasts (GF) were tested in phenol red-free, serum-free medium with or without the progestogen, medroxyprogesterone acetate (MPA; 10(-6) M), using interleukin-1beta (IL-1beta) to initiate immune responses and MMP production. These MMP responses were examined by macroarrays, reverse transcription-polymerase chain reaction (RT-PCR), zymograms, and enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Array analysis showed that pretreatment of GF with MPA reduced mRNA induction for MMPs-1, -3, and -10 in response to 6 to 8 hours incubation with IL-1beta. RT-PCR confirmed, that after 24 hours with IL-1beta , GF pretreated with MPA had undetectable levels of mRNA for MMPs-1, -2, -3, -7, -10, and -13. Zymograms of culture media from this 24-hour period showed reduction in several proteolytic activities. Examination of such 24-hour media using ELISA for MMP-3 and pro-MMP-13 confirmed that secretion of these enzymes was upregulated by IL-1beta and modulated downward by pretreatment with MPA.
  
  
  CONCLUSIONS
  Production by GF of numerous MMPs in response to IL-1beta was significantly reduced by progesterone. This steroidal modulation of proteolytic enzymes could help to explain why pregnancy gingivitis typically is not characterized by progression to periodontitis.
authors.affiliation: Department of Oral Biology, Medical College of Georgia, Augusta, GA 30912, USA. clapp@mail.mcg.edu
authors.forename: Carol A
authors.initials: CA
authors.lastname: Lapp
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Lohse
authors.forename: Jill B
authors.initials: JB
authors.lastname: Lewis
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Dickinson
authors.forename: Michael
authors.initials: M
authors.lastname: Billman
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Hanes
authors.forename: David F
authors.initials: DF
authors.lastname: Lapp
mesh_terms: D000704:Analysis of Variance; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology*; D005881:Gingiva / Q000166:cytology / Q000201:enzymology*; D006023:Glycoproteins / Q000037:antagonists & inhibitors; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D053506:Matrix Metalloproteinase 10; D053509:Matrix Metalloproteinase 13; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000235:genetics; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D011247:Pregnancy; D045167:Progesterone Congeners / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D006023:Glycoproteins; D007375:Interleukin-1; D061965:Matrix Metalloproteinase Inhibitors; D045167:Progesterone Congeners; D012333:RNA, Messenger; D017258:Medroxyprogesterone Acetate; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases; D053506:Matrix Metalloproteinase 10