Thyroid C cells produce bioregulatory peptid calcitonin (CT), which lowers plasma calcium (Ca) and acts as an inhibitor of bone resorption. In this study we investigated the effects of tamoxifen, as a selective estrogen receptor modulator on thyroid C cells and skeletal changes in middle-aged orchidectomized (Orx) rats as an animal model of male osteoporosis. Fifteen-month-old male Wistar rats were divided into Orx and a sham-operated (SO) groups. Two weeks after gonadectomy, one Orx group was injected subcutaneously (s.c.) with tamoxifen citrate (Orx+TAM; 0.03 mg/kg b.w.) for three weeks. The SO and second Orx group were treated s.c. with vehicle alone. A peroxidase-antiperoxidase (PAP) method was applied for localization of CT in the C cells. The volumes of C cells (Vc) and their volume densities (Vv) were determined using the multipurpose M42 test system. 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 and osteocalcin (OC), and urine samples for Ca concentration. We found a significant decrease in the Vc, Vv, and serum CT in Orx rats compared with the SO. Tamoxifen treatment significantly increased Vc and serum CT compared to the Orx. Analysis of trabecular microarchitecture of tibia showed that Orx induced cancellous bone loss and marked decreases of cancellous bone area (B.Ar), trabecular thickness (Tb.Th), and trabecular number (Tb.N) whereas trabecular separation (Tb.Sp) was significantly increased. Serum OC and urinary Ca concents was considerably higher in Orx rats in comparison with SO. Administration of tamoxufen significantly enhanced B.Ar, Tb.Th and Tb.N and reduced Tb.N. Serum OC and urinary Ca concentrations were significantly lower than in the Orx group. These findings indicate that tamoxifen stimulated calcitonin-producing thyroid C cells and increased trabecular bone mass in rat model of male osteoporosis.
27 Apr - 01 May 2013
European Society of Endocrinology