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However, although the bone\u2010sparing effects of genistein are achieved directly through estrogen receptors, its mode of action on bone by modulation of other endocrine functions is not entirely clear. Thus, thyroid hormones and calcitonin (<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>) have an essential influence on bone metabolism. Besides its action on bones, in this study we examined the effect of genistein on the activity of two different endocrine cell populations, thyroid follicular and C\u2010cells. Fifteen\u2010month\u2010old Wistar rats were either bilaterally orchidectomized (Orx) or sham\u2010operated (<jats:styled-content style=\"fixed-case\">SO<\/jats:styled-content>). Two weeks after surgery, half of the Orx rats were treated chronically with 30\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup> b.w. genistein (Orx\u00a0+\u00a0G) subcutaneously (s.c.) every day for 3\u00a0weeks, while the remaining Orx rats and the <jats:styled-content style=\"fixed-case\">SO<\/jats:styled-content> rats were given the same volume of sterile olive oil to serve as controls. For histomorphometrical analysis of the trabecular bone microarchitecture an <jats:sc>ImageJ<\/jats:sc> public domain image processing programme was used. Thyroid sections were analysed histologically and stereologically after visualization of follicular and C\u2010cells by immunohistochemical staining for thyroglobulin and <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>. Thyroid follicular epithelium, interstitium, colloid and <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>\u2010immunopositive C\u2010cells were examined morphometrically. Serum concentrations of osteocalcin (<jats:styled-content style=\"fixed-case\">OC<\/jats:styled-content>), triiodothyronine (T<jats:sub>3<\/jats:sub>), thyroxine (T<jats:sub>4<\/jats:sub>) and <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> were determined as well as urinary calcium (Ca<jats:sup>2+<\/jats:sup>) concentrations. Genistein treatment significantly increased cancellous bone area (B.Ar), trabecular thickness (TbTh) and trabecular number (TbN) (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), but trabecular separation (Tb.Sp) was decreased (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) compared with control Orx rats. In the thyroid, genistein treatment significantly elevated the relative volume density (Vv) of the follicular cells (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) compared with Orx, whereas Vv of the colloid was lower (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) than in the Orx. Evaluation of the biochemical parameters showed significant reductions in serum <jats:styled-content style=\"fixed-case\">OC<\/jats:styled-content>, T<jats:sub>3<\/jats:sub>, T<jats:sub>4<\/jats:sub> and urinary Ca<jats:sup>2+<\/jats:sup> concentrations (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), compared with Orx rats. These data indicate that genistein treatment improves the trabecular microarchitecture of proximal tibia, induces histomorphometrical changes in thyroid glands, and decreases circulating thyroid hormone levels in orchidectomized rat model of male osteoporosis.<\/jats:p>","DOI":"10.1111\/joa.12828","type":"journal-article","created":{"date-parts":[[2018,5,15]],"date-time":"2018-05-15T05:50:42Z","timestamp":1526363442000},"page":"204-212","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The phytoestrogen genistein prevents trabecular bone loss and affects thyroid follicular cells in a male rat model of osteoporosis"],"prefix":"10.1111","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5352-763X","authenticated-orcid":false,"given":"Branko","family":"Filipovi\u0107","sequence":"first","affiliation":[{"name":"Institute for Biological Research \u2018Sini\u0161a Stankovi\u0107\u2019 University of Belgrade 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