title: Leptin influences estrogen metabolism and accelerates prostate cell proliferation.
abstract: OBJECTIVE
  The present study was designed to investigate the effect of leptin on estrogen metabolism in prostatic cells.
  
  
  METHODS
  Malignant (PC-3) and benign (BPH-1) human prostate cells were treated with 17-β-hydroxyestradiol (1 μM) alone or in combination with leptin (0.4, 4, 40 ng/ml) for 72 h. Cell proliferation assay, immunocytochemical staining of estrogen receptor (ER), liquid chromatography-tandem mass spectrometry method (LC-MS) and semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) were used.
  
  
  RESULTS
  Cell proliferation assay demonstrated that leptin caused significant growth potentiation in both cells. Immunocytochemical staining showed that leptin significantly increased the expression of ER-α and decreased that of ER-β in PC-3 cells. LC-MS method revealed that leptin increased the concentration 4-hydroxyestrone and/or decreased that of 2-methoxyestradiol, 4-methoxyestradiol and 2-methoxyestrone. Interestingly, RT-PCR showed that leptin significantly up-regulated the expression of aromatase and cytochrome P450 1B1 (CYP1B1) enzymes; however down-regulated the expression of catechol-o-methyltransferase (COMT) enzyme.
  
  
  CONCLUSIONS
  These data indicate that leptin-induced proliferative effect in prostate cells might be partly attributed to estrogen metabolism. Thus, leptin might be a novel target for therapeutic intervention in prostatic disorders.
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Christine N
authors.initials: CN
authors.lastname: Habib
authors.affiliation: Department of Pharmacology, Medical Division, National Research Center, Dokki, Cairo, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Al-Abd
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt; Biology Department, School of Science and Engineering, The American University in Cairo, New Cairo, Egypt.
authors.forename: Mai F
authors.initials: MF
authors.lastname: Tolba
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Amani E
authors.initials: AE
authors.lastname: Khalifa
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Alaa
authors.initials: A
authors.lastname: Khedr
authors.affiliation: Department of Urology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Hisham A
authors.initials: HA
authors.lastname: Mosli
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. Electronic address: abnaim@yahoo.com.
authors.forename: Ashraf B
authors.initials: AB
authors.lastname: Abdel-Naim
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D011467:Prostate / Q000166:cytology* / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D020738:Leptin
keywords: Estrogen metabolism; Leptin; Obesity; Prostate