Nongenomic and genomic effects of 1α,25(OH)2 vitamin D3 in rat testis.

The steroid hormone 1α,25(OH)(2)-vitamin D(3) (1,25D(3)) regulates gene transcription through a nuclear receptor (VDRnuc) and initiation of rapid cellular responses through a putative plasma membrane-associated receptor (VDRmem). It has been described that successful mating and fertility rates are significantly decreased in vitamin D deficient male rats and a VDR null mutant rodent has decreased sperm count and motility and expresses rare spermatogenesis. Although the Sertoli cells are pointed as the major target of 1,25D(3) in the testis the mechanism of 1,25D(3) action, particularly in Sertoli cells, remains unclear. Several studies undertaken in the testicular cells showed that 1,25D(3) can produce both genomic and nongenotropic actions in those cells. 1,25D(3) can modulate kinase activities and ionic fluxes (Ca(2+) and Cl(-)) at the plasma membrane resulting in the regulation of secretory processes in Sertoli cells. The enormous complexity of the nongenomic actions of 1,25D(3) implies that specific receptor or specific ligand-binding sites located on the plasma membrane or in the nucleus are believed to initiate specific cell responses. Apparently the choice of the signaling pathways to be activated after the interaction of the hormone with cell surface receptors is directly related with the physiological action to be better accomplished. The demonstration that 1,25D(3) can regulate both Sertoli cell and sperm function may be useful for the study and development of new therapeutic strategies to the treatment of male reproductive disorders. This review summarizes recent research on the rapid actions of 1,25D(3) and identifies questions that remain to be answered in this area.