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; Liesbet Lieben; John E Nielsen; Ariane Willems; Anders Juul; Niels Jorgensen; Jorma Toppari; Geert Carmeliet; Meyts Ewa Rajpert-De

doi:10.1530/endoabs.32.OC2.2

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Endocrine Abstracts (2013) 32 OC2.2 | DOI: 10.1530/endoabs.32.OC2.2

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

Err

Author affiliations

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.