title: Tamoxifen stimulates calcitonin-producing thyroid C-cells and prevents trabecular bone loss in a rat model of androgen deficiency.
abstract: Thyroid C-cells produce calcitonin (CT), a hypocalcemic hormone, that acts as an inhibitor of bone resorption. In this study, we investigated the effects of tamoxifen (TAM) as a selective estrogen receptor modulator on thyroid C-cells, trabecular bone and biochemical markers of bone metabolism in an animal model of androgen deficiency, represented by middle-aged orchidectomized (Orx) rats. Fifteen-month-old male Wistar rats were divided into: Orx and sham-operated (SO) groups. Rats from one Orx group were injected subcutaneously with TAM citrate (Orx + TAM; 0.3 mg kg(-1) b.w.), while the rats from SO and a second Orx group received vehicle alone, once a day for 3 weeks. The peroxidase-antiperoxidase method was applied for localization of CT in C-cells. Thyroid C-cells were morphometrically and ultrastructurally analyzed. An ImageJ image-processing program was used to measure bone histomorphometric parameters. Blood serum samples were analyzed for CT, osteocalcin (OC), calcium (Ca2+ ) and phosphorus (P). Urinary Ca2+ concentrations were measured. TAM treatment significantly increased thyroid C-cell volume (Vc ) and serum CT when compared with vehicle-treated Orx rats. Analysis of trabecular microarchitecture of the tibia showed that administration of TAM significantly increased cancellous bone area, trabecular thickness and trabecular number, whereas trabecular separation was significantly decreased compared with vehicle-treated Orx rats. Serum OC and urinary Ca2+ concentrations were significantly lower in comparison with the control Orx group. These results indicate that in our rat model of androgen deficiency, TAM stimulated calcitonin-producing thyroid C-cells and increased trabecular bone mass.
authors: Institute for Biological Research ″Siniša Stanković″, University of Belgrade, Belgrade, Serbia.
authors: Branko
authors: B
authors: Filipović
authors: Institute for Biological Research ″Siniša Stanković″, University of Belgrade, Belgrade, Serbia.
authors: Branka
authors: B
authors: Šošić-Jurjević
authors: Institute for Biological Research ″Siniša Stanković″, University of Belgrade, Belgrade, Serbia.
authors: Vladimir
authors: V
authors: Ajdžanović
authors: Institute for Biological Research ″Siniša Stanković″, University of Belgrade, Belgrade, Serbia.
authors: Jasmina
authors: J
authors: Živanović
authors: Vinca Institute of Nuclear Science, Laboratory for Molecular Genetics and Radiobiology, University of Belgrade, Belgrade, Serbia.
authors: Esma
authors: E
authors: Isenović
authors: Faculty of Veterinary Medicine, ″Ss Cyril and Methodius″ University of Skopje, Skopje, FYR of Macedonia.
authors: Florina
authors: F
authors: Popovska-Perčinić
authors: Institute for Biological Research ″Siniša Stanković″, University of Belgrade, Belgrade, Serbia.
authors: Verica
authors: V
authors: Milošević
mesh_terms: D000704:Analysis of Variance; D000728:Androgens / Q000172:deficiency*; D000818:Animals; D002116:Calcitonin / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D007118:Immunoassay; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D009919:Orchiectomy / Q000009:adverse effects*; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000517:prevention & control*; D010758:Phosphorus / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000494:pharmacology*; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*
chemical_list: D000728:Androgens; D013629:Tamoxifen; D015675:Osteocalcin; D010758:Phosphorus; D002116:Calcitonin; D002118:Calcium
keywords: androgen deficiency; bone; calcitonin; rats; tamoxifen; thyroid C-cells