Salmon calcitonin affects thyroid endocrine cells and trabecular bone in a rat model of male osteoporosis

Abstract

Calcitonin (CT) is a hypocalcemic hormone produced by thyroid C-cells that acts as an bone antiresorptive agent. The other endocrine cell population in thyroid, called follicular cells produce thyroid hormones (TH) which also affect bone turnover. In this study, we evaluated the effects of salmon CT administration on structure and function of both CT and TH producing thyroid cells as well as trabecular bone microarchitecture in orchidectomized (Orx) middle-aged rats. Fifteen-month-old male Wistar rats were either Orx or sham-operated (SO). One group of Orx animals were injected subcutaneously with synthetic salmon CT (Orx + CT; 100 IU/kg b.w.) every second day for 6 weeks. The rats from SO and second Orx group received the same volume of vehicle alone by the same schedule. The peroxidase–antiperoxidase method was applied for localization of CT in C-cells. CT-immunopositive thyroid C-cells, thyroid follicular epithelium, interstitium and colloid were evaluated morphometrically. An ImageJ public domain image processing program was used to measure bone histomorphometric parameters of the proximal tibial specimens. Blood serum samples were analyzed for CT, osteocalcin (OC) and thyroxine (T4), and urine samples fot calcium (Ca2+) concentration. We found a significant decrease in the Vc and Vv of thyroid C-cells after CT treatment compared to both SO and Orx. The Vv of the colloid was higher, while VV of the follicular epithelium was lower after CT treatment compared to Orx. Analysis of trabecular microarchitecture showed that salmon CT administration significantly increases of cancellous bone area (B.Ar), trabecular thickness (Tb.Th), and trabecular number (Tb.N) whereas trabecular separation (Tb.Sp) was significantly decreased. CT treatment markedly elevated serum CT, but serum OC, T4 and urinary Ca2+ concentrations were lower than in the Orx group. These findings indicate that administration of salmon CT inhibited calcitonin-producing thyroid C-cells and changes the structure of the thyroid gland indicating hypoactivity.