Aromatization of androgens is important for skeletal maintenance of aged male rats
- 32 Downloads
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 dualenergy 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.
Key wordsAndrogens Bone Vorozole Aromatase Osteoporosis
Unable to display preview. Download preview PDF.
- 13.Purohit A, Flanagan AM, Reed MJ (1992) Estrogen synthesis by osteoblast cell lines. J Clin Endocrinol Metab 61:152–157Google Scholar
- 14.Vanderschueren D, Van Herck E, Suiker AMH, Visser WJ, Geusens P, Schot LPC, Bouillon R, Rush EB, Einhorn TA (1993) Bone and mineral metabolism in the androgen-resistant (testicular feminized) male rat. J Bone Miner Res 8:799–807Google Scholar
- 17.Girasole G, Jilka RL, Passeri G, Scott B, Boder G, Williams DC, Manolagas SC (1992) Estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro. A potential mechanism for the antiosteoporotic effect of estrogens. J Clin Invest 89:883–891PubMedCrossRefGoogle Scholar
- 25.Wouters W, De Coster R, Van Dun J, Krekels MDWG, Dillen A, Rayemaekers A, Freyne E, Van Gelder J, Ganz G, Venet M, Janssen M (1990) Comparative effects of the aromatase inhibitor R76713 and its enantiometers R 83839 and 83842 on steroid biosynthesis in vitro and in vivo J Steroid Biochem 37:1049–1054CrossRefGoogle Scholar
- 37.Ke-nan Qjn, Fisher CR, Grumbach MM, Morshina A, Simpson ER (1995)Aromatase deficiency in a male subject: characterization of a mutation in the CYP 19 gene in an affected family (abstract) Endocrinol Soc, 77th annual meeting, p. 475 (abstracts P3-27)Google Scholar