ECE2014 Poster Presentations Steroid metabolism and action (12 abstracts)
1Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University Graz, Graz, Austria; 2Department of Urology, Medical University Graz, Graz, Austria; 3Division of Transplantation Surgery, Department of Surgery, Medical University Graz, Graz, Austria.
Introduction: Testosterone production in male testicular cells is mainly stimulated by LH, secreted by the pituitary. Recent findings have shown significant clinical associations of vitamin D seasonal rhythms and androgens in men (Wehr et al. 2010, Nimptsch et al. 2012). We aimed to elucidate associations of vitamin D and androgen synthesis on a cellular level.
Methods: Human primary testicular cells, isolated from testes of braindead donors, and a cell line of human testis embryonal carcinoma cells (NT2/d1) were cultured in parallel and supplemented with or without luteinizing hormone (LH) in the presence or absence of 1,25-dihydroxyvitamin D (1,25OH2D). Testosterone concentrations in the culture media were measured by ELISA. Gene expression of vitamin D and androgen related genes was observed on mRNA level by RT-qPCR at baseline and after addition of physiological and supraphysiological concentrations of the hormones.
Results: At baseline, vitamin D metabolizing enzymes were expressed in both primary testicular and NT2/d1 cells. Addition of physiological doses of 1,25OH2D increased significantly mRNA levels of both androgenic genes (HSD3B1, CYP11A1, CYP19A1) and vitamin D metabolizing enzymes (CYP2R1, CYP27A1, CYP27B1) in human testicular cells, but not in NT2/d1 cells, where only vitamin D related genes were increased. Supraphysiological doses showed expression patterns similar to physiological doses, however the vitamin D catalysing enzyme CYP24A1 was significantly increased. 1,25OH2D enhanced testosterone synthesis in healthy testicular cells, but not in testicular carcinoma cells.
Conclusion: We demonstrate a significant and reproducible involvement of vitamin D in androgen synthesis in healthy testicular cells. Considering vitamin D as an important player in male androgen synthesis might help defining clinical approaches and a better therapeutic management of male hypogonadism.