Abstract
BackgroundA wider biological role of 1alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the active metabolite of vitamin D3, in tissues not primarily related to mineral metabolism was suggested. Recently, we evidenced the ultrastructural localization the 1,25(OH)2D3 receptor in the human sperm. However, the 1,25(OH)2D3 action in human male reproduction has not yet been clarified.Methods and ResultsBy RT-PCR, Western blot and Immunofluorescence techniques, we demonstrated that human sperm expresses the 1,25(OH)2D3 receptor (VDR). Besides, 25(OH)D3-1 alpha-hydroxylase, evidenced by Western blot analysis, indicated that in sperm 1,25(OH)2D3 is locally produced, highlighting the potential for autocrine-paracrine responses. 1,25(OH)2D3 through VDR, increased intracellular Ca2+ levels, motility and acrosin activity revealing an unexpected significance of this hormone in the acquisition of fertilizing ability. In sperm, 1,25(OH)2D3 through VDR, reduces triglycerides content concomitantly to the increase of lipase activity. Rapid responses stimulated by 1,25(OH)2D3 have been observed on Akt, MAPK and GSK3 implying that this secosteroid is involved in different sperm signalling pathways.ConclusionOur data extended the role of 1,25(OH)2D3 beyond its conventional physiological actions, paving the way for novel therapeutic opportunities in the treatment of the male reproduction disorders.
Highlights
A wider biological role of 1alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the active metabolite of vitamin D3, in tissues not primarily related to mineral metabolism was suggested
1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active metabolite of vitamin D3, is formed after hydroxylation by the rate-limiting enzyme 25(OH)D3-1 alphahydroxylase (1 alpha-hydroxylase), abundantly expressed in the renal proximal tubule [1]. 1,25(OH)2D3 is a secosteroid whose actions are mediated by binding to its cognate nuclear receptor, the vitamin D receptor (VDR), a
BSA protein standard, Laemmli sample buffer, prestained molecular weight markers, Percoll, Sodium bicarbonate, Sodium lactate, Sodium pyruvate, Dimethyl Sulfoxide (DMSO), Earle's balanced salt solution, 1alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3) and all other chemicals were purchased from Sigma Chemical (Milan, Italy)
Summary
A wider biological role of 1alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the active metabolite of vitamin D3, in tissues not primarily related to mineral metabolism was suggested. The VDR exerts 1,25(OH)2D3-dependent responses in the nucleus as a ligand-activated transcription factor [3]. In addition to these relatively slow genomic effects, 1,25(OH)2D3 generates rapid responses including Ca2+ uptake from intestine [4,5], augmentation of insulin secretion from pancreatic β-cells [6,7], growth and differentiation of vascular smooth muscle cells [8] and keratinocytes [9]. The VDR is widely distributed in male and female reproductive tissues [12], implying a 1,25(OH)2D3 action in these organs. The current finding evaluated the potential role of 1,25(OH)2D3/VDR system in human sperm physiology by studying its effect on Ca2+ levels, motility, acrosin activity, glucose and lipid metabolism. Rapid 1,25(OH)2D3 responses were evaluated on different signalling transductional pathways identified in sperm
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