title: Nuclear progesterone receptors in the human pregnancy myometrium: evidence that parturition involves functional progesterone withdrawal mediated by increased expression of progesterone receptor-A.
abstract: BACKGROUND
  We examined whether human parturition involves functional progesterone withdrawal mediated by changes in myometrial expression of progesterone receptors (PRs)-A and -B.
  
  
  OBJECTIVE
  Our objectives were to: 1) measure PR-A and PR-B protein levels in human pregnancy myometrium and determine whether the PR-A to PR-B ratio changes with advancing gestation and labor onset; and 2) determine how changes in the PR-A to PR-B ratio affect myometrial cell progesterone responsiveness.
  
  
  METHODS
  PR protein levels and cellular localization were measured by Western blotting and immunohistochemistry, respectively, in lower uterine segment uterine wall tissue from preterm (<37 wk; not laboring; n = 5) and term (37-40 wk; not in labor: n = 6; in labor: n = 5) cesarean delivery. The capacity for PR-A and PR-B, alone and in combination, to mediate genomic progesterone responsiveness measured by the activity of a progesterone-responsive reporter plasmid was examined by artificially modulating their levels in the PHM1-31 myometrial cell line.
  
  
  RESULTS
  PR-A and PR-B immunostaining was detected only in the nucleus of myometrial cells. The PR-A to PR-B protein ratio was 0.49 +/- 0.082 (mean +/- sem) in preterm tissue; increased to 1.03 +/- 0.071 (P < 0.001) in nonlaboring term tissue; and increased further to 2.65 +/- 0.344 (P < 0.001) in laboring term tissue. Only PR-B mediated progesterone-induced transcriptional activity. PR-A had no effect alone but markedly decreased PR-B-mediated progesterone responsiveness.
  
  
  CONCLUSIONS
  Functional progesterone withdrawal in human parturition may be mediated by an increase in the myometrial PR-A to PR-B ratio due to increased PR-A expression.
authors.affiliation: Department of Reproductive Biology, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5034, USA.
authors.forename: Amy A
authors.initials: AA
authors.lastname: Merlino
authors.forename: Toni N
authors.initials: TN
authors.lastname: Welsh
authors.forename: Huiqing
authors.initials: H
authors.lastname: Tan
authors.forename: Li Juan
authors.initials: LJ
authors.lastname: Yi
authors.forename: Vernon
authors.initials: V
authors.lastname: Cannon
authors.forename: Brian M
authors.initials: BM
authors.lastname: Mercer
authors.forename: Sam
authors.initials: S
authors.lastname: Mesiano
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009215:Myometrium / Q000166:cytology / Q000378:metabolism*; D036801:Parturition / Q000502:physiology*; D010957:Plasmids / Q000235:genetics; D011247:Pregnancy / Q000378:metabolism*; D011374:Progesterone / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000096:biosynthesis*; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B; D011374:Progesterone