Effect of gonadotropin-releasing hormone agonists, nafarelin, buserelin, and leuprolide, on experimentally induced endometriosis in the rat.
OBJECTIVE -- The purpose of this study was to compare the potency of the gonadotropin-releasing hormone (GnRH) agonists nafarelin, buserelin, and leuprolide in a newly developed model of experimental endometriosis, thus further characterizing the model. METHODS -- Endometriosis was induced in female rats by autotransplantation of endometrium to a site under the renal capsule. The effect of the GnRH agonists on explant volume and fluid accumulation was evaluated. Binding affinities of the compounds for GnRH receptors in pituitary homogenates of female rats was also measured. RESULTS -- The three GnRH agonists induced significant atrophy and regression of endometriosis. The volume of endometriosis in intact control was 26.1 +/- 4.7 cu.-mm (n = 13), 1.7 +/- 0.1 cu.-mm (n = 12) after therapy with nafarelin, 4.8 +/- 1.8 cu.- mm (n = 7) with buserelin, and 3.7 +/- 1.2 cu.-mm (n = 13) with leuprolide. The effects of these compounds were comparable to that of castration (1.9 +/- 0.5 cu.-mm; n = 10). There was no significant difference in the binding affinities of leuprolide and buserelin for pituitary GnRH receptors. CONCLUSION -- The model was found to be responsive to the GnRH agonist agents evaluated and could discriminate between dosage levels. Potency of the compound seems to correlate with binding affinity to pituitary GnRH
Mizutani
T
T
Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.
Sakata
M
M
Terakawa
N
N
D000818:Animals; D002064:Buserelin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004715:Endometriosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004717:Endometrium / Q000473:pathology / Q000637:transplantation; D004958:Estradiol / Q000097:blood; D005260:Female; D007668:Kidney; D016729:Leuprolide / Q000627:therapeutic use*; D007986:Luteinizing Hormone / Q000097:blood; D017274:Nafarelin / Q000627:therapeutic use*; D009929:Organ Size; D010053:Ovary / Q000473:pathology; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011966:Receptors, LHRH / Q000378:metabolism; D014599:Uterus / Q000473:pathology
D011966:Receptors, LHRH; D017274:Nafarelin; D004958:Estradiol; D007986:Luteinizing Hormone; D016729:Leuprolide; D002064:Buserelin