The effects of sex steroids on thyroid C cells and trabecular bone structure in the rat model of male osteoporosis

Abstract

Androgen deficiency is one of the major factors leading to the development of osteoporosis in men. Since calcitonin (CT) is a potent antiresorptive agent, in the present study we investigated the effects of androgen deficiency and subsequent testosterone and estradiol treatment on CT-producing thyroid C cells, skeletal and hormonal changes in middle-aged orchidectomized (Orx) rats. Fifteen-month-old male Wistar rats were either Orx or sham-operated (SO). One group of Orx rats received 5 mg kg À1 b.w. testosterone propionate (TP) subcutaneously, while another group was injected with 0.06 mg kg À1 b.w. estradiol dipropionate (EDP) once a day for 3 weeks. A peroxidase-antiperoxidase method was applied for localization of CT in the C cells. The studies included ultrastructural microscopic observation of these cells. The metaphyseal region of the proximal tibia was measured histomorphometrically using an IMAGEJ public domain image processing program. TP or EDP treatment significantly increased C cell volume (Vc), volume densities (Vv) and serum CT concentration compared with the Orx animals. Administration of both TP and EDP significantly enhanced cancellous bone area (B.Ar), trabecular thickness (Tb.Th) and trabecular number (Tb.N) and reduced trabecular separation (Tb.Sp). Serum osteocalcin (OC) and urinary Ca concentrations were significantly lower after these treatments in comparison with Orx rats. These data suggest that testosterone and estradiol treatment in Orx middle-aged rats affect calcitonin-producing thyroid C cells, which may contribute to the bone protective effects of sex hormones in the rat model of male osteoporosis.

The effects of orchidectomy and supraphysiological testosterone administration on trabecular bone structure and gene expression in rats

“…Testosterone deficiency either due to late-onset hypogonadism or androgen deprivation therapy is the major cause of male osteoporosis [3,4]. Testosterone deficiency due to orchidectomy has been found to cause degenerative changes in trabecular structure in animal models of osteoporosis [5,6]. Thus, the orchidectomized rat model has been used as a standard male hypogonadal osteoporosis model in the screening of antiosteoporotic agents [7].…”

Tamoxifen stimulates calcitonin‐producing thyroid C‐cells and prevents trabecular bone loss in a rat model of androgen deficiency

“…Administration of estradiol or testosterone to Orx rats stimulated the secretory activity of thyroid C‐cells (Filipović et al. ).…”

“…Immunocytochemically stained C-cells in the central part of each rat thyroid were stereologically analyzed by a point-counting method described by Filipovi c et al (2007), using a M42 multipurpose test grid inserted into the ocular of a Zeiss light microscope (Jena, Germany). The cell volume of thyroid C-cells (V c ) and their volume density (V V ) were estimated on 50 test fields per section at 1000 9 magnification.…”

“…; Yamazaki & Kinoshita, ; Filipović et al. , ). Clinical investigations indicate that, together with the lack of testosterone, estrogen deficiency plays an important role in age‐related bone loss in elderly men (Slemenda et al.…”

“…In the state of gonadal steroid deficiency, an appropriate estrogen or testosterone administration has bone-protective effects and stimulates the activity of CT-producing thyroid C-cells in rats (Catherwood et al 1983;Yamazaki & Kinoshita, 1986;Filipovi c et al 2003Filipovi c et al , 2013. Clinical investigations indicate that, together with the lack of testosterone, estrogen deficiency plays an important role in age-related bone loss in elderly men (Slemenda et al 1997).…”