title: Response of trabecular bone, thyroid C and follicular cells to synthetic salmon calcitonin in middle-aged orchidectomized male rats.
abstract: In contrast to studies in women, male osteoporosis is poorly understood and strictly related to advancing age. Among the first antiresorptive substances used in the prevention and treatment of osteoporosis is calcitonin (CT), a hypocalcemic hormone that potently inhibits osteoclastic bone resorption. Natural CT is produced and secreted by thyroid C-cells. The other endocrine population of thyroid cells produces thyroid hormones (TH), which also affect bone turnover. The aim of this study was to evaluate the influence of salmon CT on trabecular bone microarchitecture with special reference to effects on the structure and function of both CT- and TH-producing thyroid cells in orchidectomized (Orx) middle-aged rats. Twenty-four male Wistar rats aged 15 months were randomly divided into Orx and sham-operated (SO) groups. One group of Orx animals received (s.c.) synthetic salmon CT (Orx + CT; 100 IU kg-1b.w.) subcutaneously every second day for 6 weeks. The second Orx group and SO rats were given the same volume of vehicle alone by the same schedule. Trabecular bone histomorphometrical parameters were: cancellous bone area (B.Ar), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) were obtained with an ImageJ public-domain image-processing program. The peroxidase-antiperoxidase method was applied for localization of CT in C-cells. Anti-human CT antisera served as the primary antibodies. For immunohistochemical characterization of vascular endothelial growth factor (VEGF) in thyroid tissue, rabbit antisera against human VEGF, served as primary antibodies. CT-immunopositive thyroid C-cells, thyroid follicular epithelium, interstitium and colloid were evaluated morphometrically. Blood serum samples were analyzed for CT, osteocalcin (OC), and thyroxine (T4), and calcium (Ca2+) concentration was determined in urine samples. Salmon CT application significantly increased B.Ar, TbTh and TbN, but markedly decreased Tb.Sp. Administration of exogenous CT significantly decreased mean volume (Vc) and relative volume density (Vv) of thyroid C-cells in relation to both SO and Orx groups. The Vv of the colloid was higher, whereas the VVof the follicular epithelium was lower after CT treatment compared with Orx alone. CT treatment markedly elevated serum CT, whereas serum OC, T4and urinary Ca2+concentrations were lower than in the Orx group. These results indicate that salmon CT stimulates trabecular bone microarchitecture, strongly inhibits thyroid C-cells and changes the structure of the thyroid gland, indicating hypoactivity.
authors.affiliation: Department of Cytology, Institute for Biological Research 'Siniša Stanković' University of Belgrade, Belgrade, Serbia.
authors.forename: Branko
authors.initials: B
authors.lastname: Filipović
authors.affiliation: Department of Cytology, Institute for Biological Research 'Siniša Stanković' University of Belgrade, Belgrade, Serbia.
authors.forename: Branka
authors.initials: B
authors.lastname: Šošić-Jurjević
authors.affiliation: Department of Cytology, Institute for Biological Research 'Siniša Stanković' University of Belgrade, Belgrade, Serbia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Ajdžanović
authors.affiliation: Department of Cytology, Institute for Biological Research 'Siniša Stanković' University of Belgrade, Belgrade, Serbia.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Živanović
authors.affiliation: Department of Cytology, Institute for Biological Research 'Siniša Stanković' University of Belgrade, Belgrade, Serbia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Ristić
authors.affiliation: Department of Cytology, Institute for Biological Research 'Siniša Stanković' University of Belgrade, Belgrade, Serbia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Trifunović
authors.affiliation: Department of Cytology, Institute for Biological Research 'Siniša Stanković' University of Belgrade, Belgrade, Serbia.
authors.forename: Verica
authors.initials: V
authors.lastname: Milošević
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002116:Calcitonin / Q000494:pharmacology*; D000071556:Cancellous Bone / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009919:Orchiectomy; D051381:Rats; D017208:Rats, Wistar; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D050071:Bone Density Conservation Agents; D042461:Vascular Endothelial Growth Factor A; C028815:salmon calcitonin; D002116:Calcitonin
keywords: bone; calcitonin; osteoporosis; rat; thyroid C-cells; thyroid follicular cells