科研之友
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摘要
The spectrum for vitamin D (VD) mediated effects has expanded in recent years. Activated VD (1,25(OH)(2)D-3) binds to the VD receptor (VDR) and mediates non-genomic effects through the alternative ligand binding-pocket (VDR-ap) or regulates gene transcription through the genomic binding-pocket. VDR and VD-metabolizing enzymes are expressed in human testis, male reproductive tract and mature spermatozoa, and VD is considered important for male reproduction. Expression of the VD-inactivating enzyme CYP24A1 at the annulus of human spermatozoa distinguish normal and infertile men with high specificity, and CYP24A1 expression is positively correlated with all semen variables and suggested as a marker for both semen quality and VD responsiveness. Moreover, spermatozoa are transcriptionally silent and are therefore a unique model to study non-genomic effects. 1,25(OH)(2)D-3 induced a rapid increase in intracellular calcium concentration [Ca2+] in human spermatozoa. The [Ca2+] increase was abrogated by the non-genomic VDR antagonist 1 beta,25(OH)(2)D-3, while the specific agonist for VDR-ap (JN) increased [Ca2+]; with similar kinetics as 1,25(OH)(2)D-3. The rise in [Ca2+]; originated as a Ca2+-release from intracellular stores since inhibition of phospholipase-C diminished the 1,25(OH)(2)D-3 mediated Ca2+ response, while suspending spermatozoa in a nominally Ca2+-free medium did not affect the VD mediated Ca2+ rise. The spatio-temporal kinetics of the VD-response differed from the progesterone-mediated increase in [Ca2+]; as the VD-mediated Ca2+ rise was not observed in the tail region and was independent of extracellular Ca2+. A functional role of the VD-mediated Ca2+ increase was supported by showing that 1,25(OH)(2)D-3 increased sperm motility and induced the acrosome reaction in vitro.
- 出版日期2012-8
