Aromatization of androgens is important for skeletal maintenance of aged male rats.
A nonsteroidal aromatase inhibitor vorozole (VOR) was administered to aged (12 months old) male Wistar rats and its effect was compared with the effect of androgen deficiency. The rats were either sham-operated (SHAM) or orchidectomized (ORCH) and treated with or without VOR. Thus, four experimental groups were created (SHAM, ORCH, SHAM + VOR, ORCH + VOR). The follow-up period was 4 months. At the end of the experimental period, bone mineral density (BMD) of the first four lumbar vertebrae and right femur was measured ex vivo with dual-energy X-ray absorptiometry, bone formation was evaluated by serum osteocalcin, and bone resorption by urinary excretion of (deoxy)pyridinoline. Orchidectomy increased bone resorption 2- to 3-fold whereas bone formation was only slightly increased. Treatment of intact male rats with VOR also increased bone resorption (+30% increase) whereas bone formation was not increased in this SHAM + VOR group. Their BMD was 7% lower in the femur (P < 0.01) and 6% lower in the lumbar vertebrae (P < 0.01) compared with the SHAM group that had not received VOR. Moreover, this decrease of bone mineral density was not significantly different from the expected decrease of bone density observed in the ORCH groups (6-10%). This was also reflected by a decrease of calcium content of the first four lumbar vertebrae of 15% (P < 0.001) in the SHAM + VOR group and 9-14% (P < 0.05) in the ORCH groups compared with the SHAM group, respectively. These data therefore suggest that inhibition of aromatization of androgens into estrogens increases bone resorption and bone loss similar to that observed after complete removal of androgens. Aromatization of androgens into estrogens may therefore, at least partly, explain the effects of androgens on skeletal maintenance.
Vanderschueren
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Laboratorium voor Experimentele Geneeskunde en Endocrinologie (LEGENDO), Onderwijs en Navorsing, Gasthuisberg, B-3000 Leuven, Belgium.
Van Herck
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De Coster
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Bouillon
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D015502:Absorptiometry, Photon; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000596:Amino Acids / Q000652:urine; D000704:Analysis of Variance; D000728:Androgens / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D047072:Aromatase Inhibitors; D015519:Bone Density / Q000187:drug effects*; D001846:Bone Development / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy / Q000652:urine; D002118:Calcium / Q000032:analysis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004967:Estrogens / Q000737:chemistry; D005269:Femur / Q000187:drug effects / Q000502:physiology; D008159:Lumbar Vertebrae / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D008297:Male; D009919:Orchiectomy; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000596:Amino Acids; D000728:Androgens; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004967:Estrogens; D014230:Triazoles; D015675:Osteocalcin; C060523:vorozole; C036020:deoxypyridinoline; D002118:Calcium