Human male gamete endocrinology: 1alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates different aspects of human sperm biology and metabolism.
BACKGROUND
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. 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.


RESULTS
By 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.


CONCLUSIONS
Our 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.
Aquila
Saveria
S
Dept Pharmaco-Biology, University of Calabria 87036 Arcavacata di Rende, Cosenza, Italy. aquisav@libero.it
Guido
Carmela
C
Middea
Emilia
E
Perrotta
Ida
I
Bruno
Rosalinda
R
Pellegrino
Michele
M
Andò
Sebastiano
S
D000176:Acrosin / Q000378:metabolism; D042964:Acyl-CoA Dehydrogenase / Q000378:metabolism; D000328:Adult; D015153:Blotting, Western; D002117:Calcitriol / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D004789:Enzyme Activation / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D005854:Germ Cells / Q000378:metabolism / Q000502:physiology*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008049:Lipase / Q000378:metabolism; D008297:Male; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D018167:Receptors, Calcitriol / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013081:Sperm Motility / Q000502:physiology; D013094:Spermatozoa / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D014280:Triglycerides / Q000378:metabolism
D018167:Receptors, Calcitriol; D014280:Triglycerides; D012313:RNA; D005954:Glucosephosphate Dehydrogenase; D042964:Acyl-CoA Dehydrogenase; D008049:Lipase; D000176:Acrosin; D002117:Calcitriol; D002118:Calcium