title: Changes in proliferating and apoptotic markers of leiomyoma following treatment with a selective progesterone receptor modulator or gonadotropin-releasing hormone agonist.
abstract: OBJECTIVE
  To evaluate changes in proliferating and apoptotic markers of myoma tissue from patients treated with a selective progesterone receptor modulator (SPRM) or GnRH agonist by measuring expression of PDGF-A mRNA, IGF-1 mRNA, bcl-2 mRNA, and PCNA and caspase-3 protein.
  
  
  METHODS
  Between December 2013 and July 2014, women with symptomatic leiomyoma were divided into control (no treatment before surgery), SPRM (treatment with ulipristal acetate [SPRM] for 3 months before surgery), and GnRHa (treatment with leuprolide acetate [GnRH agonist] for 3 months before surgery) groups. Tissue specimens were collected from the myoma core and normal myometrium of all patients. The expression of mRNA and protein was assessed by quantitative real-time reverse transcriptase-polymerase chain reaction and Western blot.
  
  
  RESULTS
  A total of 38 patients were enrolled (control group, n=14; SPRM group, n=13; GnRHa group, n=11). PDGF-A mRNA expression was lower in both the myoma core and normal myometrium tissues of the SPRM compared with the control group, but there was no difference between the control and GnRHa group. There were also no group differences in bcl-2 mRNA or IGF-1 mRNA expression. Both PCNA and caspase-3 protein expression were higher in the leiomyoma tissue of the SPRM compared with the control group, but there was no difference between the control and GnRHa groups in the expression of either protein.
  
  
  CONCLUSIONS
  Both proliferation and apoptosis were increased in the leiomyoma of patients after SPRM treatment, but there was no change following GnRH agonist treatment, in vivo. However, PDGF-A mRNA was decreased after SPRM treatment, indicating a dual effect of progesterone on the regulation of growth factors. Furthermore, there was an increase in caspase-3 protein, but not bcl-2 mRNA, expression in the SPRM group suggesting that SPRM may exert its effects in pathways other than the bcl-2 apoptotic pathway.
authors.affiliation: Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University, Seoul, Republic of Korea.
authors.forename: Bo Seong
authors.initials: BS
authors.lastname: Yun
authors.affiliation: Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University, Seoul, Republic of Korea. Electronic address: sjseongcheil@gmail.com.
authors.forename: Seok Ju
authors.initials: SJ
authors.lastname: Seong
authors.affiliation: Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University, Seoul, Republic of Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Cha
authors.affiliation: Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University, Seoul, Republic of Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University, Seoul, Republic of Korea.
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Kim
authors.affiliation: Department of Pathology, CHA Gangnam Medical Center, CHA University, Seoul, Republic of Korea.
authors.forename: Jeong Yun
authors.initials: JY
authors.lastname: Shim
authors.affiliation: Genetics Laboratory, Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul, Republic of Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Park
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003131:Combined Modality Therapy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D016729:Leuprolide / Q000627:therapeutic use; D008875:Middle Aged; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D009363:Neoplasm Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009649:Norpregnadienes / Q000627:therapeutic use; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011966:Receptors, LHRH / Q000819:agonists* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery
chemical_list: D018931:Antineoplastic Agents, Hormonal; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; C484844:GNRHR protein, human; D009363:Neoplasm Proteins; D009649:Norpregnadienes; D018809:Proliferating Cell Nuclear Antigen; D011966:Receptors, LHRH; D011980:Receptors, Progesterone; D020796:Receptor, Platelet-Derived Growth Factor alpha; C505407:CASP3 protein, human; D053148:Caspase 3; D016729:Leuprolide; C555622:ulipristal acetate
keywords: Apoptosis; GnRH agonist; Leiomyoma; Proliferation; SPRM