title: Expression of a mitochondrial progesterone receptor (PR-M) in leiomyomata and association with increased mitochondrial membrane potential.
abstract: BACKGROUND
  Clinical evidence supports a role for progestins in the growth of leiomyomata (fibroids). The mechanism(s) for this is thought to involve gene regulation via the nuclear progesterone receptors. Recently a mitochondrial progesterone receptor (PR-M) has been identified with evidence of a progesterone/progestin-dependent increase in cellular respiration. This observation raises a possible new mechanism whereby progesterone/progestin may affect the growth of fibroids.
  
  
  OBJECTIVE
  The goals of this research were to determine differential expression of PR-M in normal myometrium compared with the edge of a fibroid within the same uterus, to demonstrate a progestin-dependent increase in mitochondria membrane potential using an immortalized human myometrial cell line and to examine mitochondrial membrane potential in transfected cells expressing the complete coding sequence of PR-M.
  
  
  METHODS
  Protein levels of PR-M, PR-B, PR-A, mitochondrial porin, and glyceraldehyde-3-phosphate dehydrogenase were determined in the myometrium and adjacent edge of a fibroid in 10 subjects undergoing hysterectomy for benign indications. Mitochondrial membrane potential was determined by fluorescent emission of 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolecarbocyanide iodine in hTERT-HM cells treated with R5020 and in transfected hTERT-HM cells determined by the fluorescent emission of tetramethylrhodamine methyl ester.
  
  
  RESULTS
  Higher levels of PR-M and mitochondrial porin were found in the fibroid edge compared with adjacent myometrium. Progestin increased mitochondrial membrane potential in hTERT-HM cells, which was not affected by a translation inhibitor. This effect was exaggerated in hTERT-HM cells expressing PR-M after transient transfection.
  
  
  CONCLUSIONS
  These studies suggest a mechanism whereby progesterone/progestin may affect the growth of fibroids by altering mitochondrial activity.
authors.affiliation: Department of Obstetrics and Gynecology (Q.F.), The First Affiliated Hospital, Zhengzhou University, Henan Zhengzhou, China 450052; and Department of Obstetrics and Gynecology (J.R.C., Q.D., P.C.L., T.M.P.), Division of Reproductive Endocrinology and Infertility, and Department of Pathology (P.C.L.), Duke University Medical Center, Duke University, Durham, North Carolina 27713.
authors.forename: Quanling
authors.initials: Q
authors.lastname: Feng
authors.forename: John R
authors.initials: JR
authors.lastname: Crochet
authors.forename: Qunsheng
authors.initials: Q
authors.lastname: Dai
authors.forename: Phyllis C
authors.initials: PC
authors.lastname: Leppert
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Price
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics*; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000235:genetics / Q000378:metabolism*; D009215:Myometrium / Q000378:metabolism / Q000473:pathology; D011372:Progestins / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D011372:Progestins; D011980:Receptors, Progesterone