title: Estrogen receptor (ER)-α, β and progesterone receptor (PR) mediates changes in relaxin receptor (RXFP1 and RXFP2) expression and passive range of motion of rats' knee.
abstract: OBJECTIVE
  The high risk of knee injuries in female may be associated with sex-steroid hormone fluctuations during the menstrual cycle by its effect on ligaments and tendons stiffness. This study examined changes in knee range of motion in presence of estrogen and progesterone and investigated the interaction of their antagonists to relaxin receptors.
  
  
  METHODS
  Sixty WKY rats were divided into 10 different groups receiving 17β-estradiol (0.2, 2, 20 and 50 μg/kg), progesterone (4 mg/kg), estrogen receptor (ER) antagonist ICI 182/780, ERβ antagonist PHTPP, ERα antagonist MPP, and mifepristone in presence of estrogen and progesterone. Physiologic dose were injected subcutaneously 30 min before of hormone injection for 3 days consequently. Sham group received peanut oil (vehicle) also for 3 consecutive days. Following the treatment administrations, the knee range of motion and RXFP1/RXFP2 mRNA and protein expression were examined in the patellar tendon, lateral collateral ligament, and hamstring muscle.
  
  
  RESULTS
  Our data showed that the knee range of motion was significantly increased in progesterone and high doses estrogen treatment but not significantly increased in low doses of estrogen treatment. The range of motion was decreased in the presence of estrogen receptor (ER) antagonist ICI 182/780, ERβ antagonist PHTPP, ERα antagonist MPP, and mifepristone, independently.
  
  
  CONCLUSIONS
  Progesterone and high doses of estrogen treatment resulted in the highest range of knee laxity correlated to expression of both relaxin receptor isoforms in knee tissues. Our findings thus suggested that female subjects are more vulnerable toward non-traumatic knee injury due to estrogen and progesterone fluctuation as compared to male subjects.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Exercise Science, Sports Centre, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: fir_dhn@yahoo.com.
authors.forename: Firouzeh
authors.initials: F
authors.lastname: Dehghan
authors.affiliation: Department of Exercise Science, Sports Centre, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Ashril
authors.initials: A
authors.lastname: Yusof
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Sekaran
authors.initials: S
authors.lastname: Muniandy
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: naguib.salleh@yahoo.com.
authors.forename: Naguib
authors.initials: N
authors.lastname: Salleh
mesh_terms: D000818:Animals; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D006614:Hindlimb / Q000187:drug effects* / Q000502:physiology; D008297:Male; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology; D016059:Range of Motion, Articular / Q000187:drug effects*; D051381:Rats; D011921:Rats, Inbred WKY; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D018000:Receptors, Peptide / Q000235:genetics* / Q000378:metabolism; D013256:Steroids / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: C524478:1,3-bis(4-hydroxyphenyl)-4-methyl-5-(4-(2-piperidinylethoxy)phenol)-1H-pyrazole; C556295:4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo(1,5-a)pyrimidin-3-yl)phenol; D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C504789:Rxfp1 protein, rat; C511608:Rxfp2 protein, rat; D013256:Steroids; D000077267:Fulvestrant; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol
keywords: Estrogen; Knee laxity; Progesterone; Relaxin receptor