Sex-steroid regulation of relaxin receptor isoforms (RXFP1 & RXFP2) expression in the patellar tendon and lateral collateral ligament of female WKY rats.
The incidence of non-contact knee injury was found higher in female than in male and is related to the phases of the menstrual cycle. This raised the possibility that female sex-steroids are involved in the mechanism underlying this injury via affecting the expression of the receptors for relaxin, a peptide hormone known to modulate ligament laxity. Therefore, this study aims to investigate the effect of sex-steroids on relaxin receptor isoforms (RXFP1 & RXFP2) expression in the ligaments and tendons of the knee.


METHODS
Ovariectomized adult female WKY rats were treated with different doses of estrogen (0.2, 2, 20 μg/kg), progesterone (4mg) and testosterone (125 & 250μg/kg) for three consecutive days. At the end of the treatment, the animals were sacrificed and the patellar tendon and lateral collateral ligament were harvested for mRNA and protein expression analyses by Real Time PCR and Western blotting respectively.


RESULTS
RXFP1, the main isoform expressed in these knee structures and RXFP2 showed a dose-dependent increase in expression with estrogen. Progesterone treatment resulted in an increase while testosterone caused a dose-dependent decrease in the mRNA and protein expression of both relaxin receptor isoforms.


CONCLUSIONS
Progesterone and high dose estrogen up-regulate while testosterone down-regulates RXFP1 and RXFP2 expression in the patellar tendon and lateral collateral ligament of rat's knee.


CONCLUSIONS
Relaxin receptor isoforms up-regulation by progesterone and high dose estrogen could provide the basis for the reported increase in knee laxity while down-regulation of these receptor isoforms by testosterone could explain low incidence of non-contact knee injury in male.
1. Department of Physiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;
Firouzeh
F
Dehghan
2. Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;
Sekaran
S
Muniandy
3. Department of Physiology, Sport Center, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Ashril
A
Yusof
1. Department of Physiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;
Naguib
N
Salleh
D000818:Animals; D004967:Estrogens / Q000008:administration & dosage; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000008:administration & dosage*; D006801:Humans; D007718:Knee Injuries / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017844:Lateral Ligament, Ankle / Q000378:metabolism; D008297:Male; D017847:Patellar Ligament / Q000378:metabolism; D011374:Progesterone / Q000008:administration & dosage; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics; D018000:Receptors, Peptide / Q000096:biosynthesis* / Q000235:genetics; D013739:Testosterone / Q000008:administration & dosage
D004967:Estrogens; D012739:Gonadal Steroid Hormones; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C504789:Rxfp1 protein, rat; C511608:Rxfp2 protein, rat; D013739:Testosterone; D011374:Progesterone
RXFP1; RXFP2; collateral ligaments.; patellar tendon; sex-steroids