title: Localization and hormonal regulation of endometrial matrix metalloproteinase-26 in the rhesus macaque.
abstract: BACKGROUND
  The current understanding of hormonal regulation of matrix metalloproteinase-26 (MMP-26) in the primate endometrium is incomplete. The goal of this work was to clarify estrogen and progesterone regulation of MMP-26 in the endometrium of ovariectomized, hormone-treated rhesus macaques.
  
  
  METHODS
  Ovariectomized rhesus macaques (n= 66) were treated with estradiol (E(2)), E(2) plus progesterone, E(2) followed by progesterone alone or no hormone. Endometrium was collected from the hormone-treated animals during the early, mid- and late proliferative and secretory phases of the artificial menstrual cycle. MMP-26 expression was quantified by real-time PCR, and MMP-26 transcript and protein were localized by in situ hybridization and immunohistochemistry and correlated with estrogen receptor 1 and progesterone receptor (PGR).
  
  
  RESULTS
  MMP-26 was localized to glandular epithelium and was undetectable in the endometrial stroma and vasculature. MMP-26 transcript levels were minimal in the hormone-deprived macaques and treatment with E(2) alone did not affect MMP-26 levels. Treatment with progesterone both in the presence and absence of E(2) stimulated MMP-26 expression in the early and mid-secretory phases (P < 0.001). MMP-26 expression preceded decidualization of endometrial stroma. MMP-26 levels then declined to baseline in the late secretory phase (P < 0.01) despite continued E(2) plus progesterone treatment. Loss of detectable MMP-26 expression in the late secretory phase was correlated with late secretory phase loss of glandular epithelial PGR.
  
  
  CONCLUSIONS
  Endometrial MMP-26 expression is dependent on the presence of progesterone in the early secretory phase and then gradually becomes refractory to progesterone stimulation in the late secretory phase. In the macaque, MMP-26 is a marker of the pre-decidual, secretory endometrium. During the second half of the late secretory phase, and during decidualization, MMP-26 loses its response to progesterone concurrent with the loss of epithelial PGR. The decline in MMP-26 levels between the mid- and late secretory phases may play a role in the receptive window for embryo implantation.
authors.affiliation: Department of Anatomy, Institute of Biosciences, Univ Estadual Paulista, Botucatu, São Paulo, Brazil.
authors.forename: C C D
authors.initials: CC
authors.lastname: Almeida-Francia
authors.forename: C S
authors.initials: CS
authors.lastname: Keator
authors.forename: K
authors.initials: K
authors.lastname: Mah
authors.forename: L
authors.initials: L
authors.lastname: Holden
authors.forename: C
authors.initials: C
authors.lastname: Hergert
authors.forename: O D
authors.initials: OD
authors.lastname: Slayden
mesh_terms: D000818:Animals; D004717:Endometrium / Q000201:enzymology*; D004848:Epithelium / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007150:Immunohistochemistry; D008253:Macaca mulatta; D053505:Matrix Metalloproteinases, Secreted / Q000032:analysis* / Q000235:genetics*; D008597:Menstrual Cycle / Q000502:physiology; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D011980:Receptors, Progesterone / Q000032:analysis
chemical_list: D012333:RNA, Messenger; D011980:Receptors, Progesterone; D011374:Progesterone; D004958:Estradiol; D053505:Matrix Metalloproteinases, Secreted