ECE2013 Oral Communications Bone & Calcium (6 abstracts)
Influence of vitamin D and calcium on reproductive hormones: a study in a VDR-ablated male mouse model and 300 healthy men
Martin Blomberg Jensen 1 , Liesbet Lieben 2 , John E Nielsen 1 , Ariane Willems 2 , Anders Juul 1 , Niels Jørgensen 1 , Jorma Toppari 3 , Geert Carmeliet 2 & Ewa Rajpert-De Meyts 1
1Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark; 2Clinical and Experimental Endocrinology, KU, Leuven, Belgium; 3Departments of Physiology and Paediatrics, University of Turku, Turku, Finland.
Introduction: Vitamin D (VD) is metabolized locally in the testis, and ablation of the VD receptor (Vdr−/−) in mice has proven a valid model for hereditary VD resistant rickets. However, only one of three published Vdr−/− strains presented with male infertility. Here, we investigated reproductive hormones, gene expression and the testicular histological phenotype of male Vdr−/−mice, and associated these results with reproductive hormone levels of men with different VD status.
Material and methods: In total 9 wildtype Vdr+/+, 8 Vdr−/+, and 11 Vdr−/− mice were investigated at the age of 10 and 15 weeks. Histology and gene-expression were examined in murine testis tissue by q-PCR and immunohistochemistry. Murine serum gonadotropins, testosterone and estradiol were measured with immunoassays. Serum levels of 25-hydroxyVD and calcium were subsequently established in a cross-sectional study of 300 men from the general population and associated with serum concentrations of estradiol, testosterone, Inhibin B, SHBG, LH and FSH.
Results: Testicular histology was grossly normal in Vdr−/−mice without differences in tubular diameter, epithelial width or Leydig cell-numbers. No changes were found in serum hormone levels and accordingly, no difference in expression of Cyp19a1, Erα, 17-βhsd, Star, Inhibin B, and Amh. However, a significantly lower expression of Erβ in testis and epididymis (P<0.05) was found in Vdr−/− and Vdr−/+. In the human study, 44% were VD insufficient (<50 nM), and 25-hydroxyVD correlated positively with SHBG and negatively with free androgen index (FAI) (P<0.05), while albumin-corrected calcium had the opposite effect. Adjusted regression analyses confirmed the associations of VD and calcium with SHBG and FAI (P<0.05).
Conclusion: VD is apparently dispensable for testicular hormone biosynthesis in mice and humans, but may be regulating Erβ expression in murine testis and epididymis. The associations between serum 25-hydroxyVD and calcium with SHBG /FAI in men indicate a systemic rather than testicular effect of VD.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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