The selective estrogen receptor modulator SCH 57068 prevents bone loss, reduces serum cholesterol and blocks estrogen-induced uterine hypertrophy in ovariectomized rats.
Our objective was to determine the effects of SCH 57068 alone and with 17 beta-estradiol (E(2)) on bone, lipids and uteri in ovariectomized (OVX) rats. In OVX animals lumbar vertebral and femoral bone mineral density (BMD) were significantly higher after 12 weeks of treatment with SCH 57068 than in untreated OVX controls. Similarly BMD was superior in OVX + E(2) + SCH 57068 treated animals than in OVX + E(2) controls. SCH 57068 also significantly reduced the increase in bone turnover markers, serum pyridinoline and serum osteocalcin levels, induced by OVX, and increased mechanical bone strength. SCH 57068 also significantly reduced the rise in serum cholesterol and low-density lipoprotein cholesterol induced by OVX. SCH 57068 had no stimulatory effect on uterine epithelium when given alone in OVX rats. SCH 57068 (1 and 2.5 mg/kg) reduced uterine weight and blocked endometrial stimulation induced by E(2). In summary, SCH 57068 adds to the positive effects of E(2) on bone and lipid metabolism but blocks the stimulatory effects of E(2) on the uterus. Potentially, E(2) + SCH 57068 could be combined for the treatment and prevention of breast cancer or as a novel hormone replacement therapy.
Goss
Paul E
PE
Breast Cancer Prevention Program, Princess Margaret Hospital, University Health Network, University of Toronto, Ontario, Canada M5G 2M9. pegoss@interlog.com
Qi
Shangle
S
Cheung
Angela M
AM
Hu
Haiqing
H
Mendes
Maria
M
Pritzker
Kenneth P H
KP
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D002784:Cholesterol / Q000097:blood*; D004195:Disease Models, Animal; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005269:Femur / Q000187:drug effects / Q000502:physiology; D006984:Hypertrophy / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000502:physiology; D015394:Molecular Structure; D009929:Organ Size; D010024:Osteoporosis / Q000473:pathology / Q000517:prevention & control*; D010052:Ovariectomy; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology* / Q000627:therapeutic use; D014599:Uterus / Q000187:drug effects* / Q000473:pathology*; D015430:Weight Gain / Q000187:drug effects
D015415:Biomarkers; D004965:Estrogen Antagonists; D004967:Estrogens; D010880:Piperidines; D020845:Selective Estrogen Receptor Modulators; C012121:ritetronium; D002784:Cholesterol