Testosterone inhibits osteoclast formation stimulated by parathyroid hormone through androgen receptor.
Androgens play an important role in the regulation of bone metabolism in animals and humans. The present study was performed to investigate whether androgens would affect osteoclast formation stimulated by parathyroid hormone (PTH) in mouse bone cell cultures and its mechanism. Testosterone as well as alpha-dihydrotestosterone (DHT) concentration-dependently inhibited osteoclast formation induced by PTH-(1-34). 10(-8) M ICI 182780, an estrogen receptor inhibitor, did not affect PTH-induced osteoclast formation antagonized by 10(-8) M testosterone, although it completely antagonized the effects of 10(-8) M 17beta-estradiol. Moreover, 3 microM 4-androsten-4-ol-3,17-dione, an aromatase inhibitor, did not affect PTH-induced osteoclast formation antagonized by testosterone. Hydroxyflutamide, an androgen receptor antagonist, concentration-dependently antagonized the inhibitory effects of testosterone as well as DHT on PTH-stimulated osteoclast formation. In conclusion, the present study first demonstrated that testosterone inhibited osteoclast formation stimulated by PTH through the androgen receptor, but not through the production of intrinsic estrogen in mouse bone cell cultures.
Third Division, Department of Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, 650, Kobe, Japan.
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Chen
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Kaji
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Sugimoto
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Chihara
D000726:Androgen Antagonists / Q000494:pharmacology; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D047072:Aromatase Inhibitors; D002455:Cell Division; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005485:Flutamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077267:Fulvestrant; D005965:Glucuronates / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000502:physiology*; D011944:Receptors, Androgen / Q000502:physiology*; D019379:Teriparatide / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology / Q000502:physiology*
C409215:17-glucuronosylestradiol; D000726:Androgen Antagonists; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D005965:Glucuronates; D010281:Parathyroid Hormone; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D019379:Teriparatide; D000077267:Fulvestrant; C014290:hydroxyflutamide; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D005485:Flutamide; C014594:formestane