Functional Importance of 1α,25(OH)2-Vitamin D3 and the Identification of Its Nongenomic and Genomic Signaling Pathways in the Testis

Abstract

The 1α,25(OH)2-vitamin D3 (1,25-D3) is known by its classic effects on Ca2+ metabolism and regulation of cellular proliferation and differentiation. The hormone 1,25-D3 acts in the testis through nongenomic and genomic events being implicated in the success of spermatogenesis in rats and in human being. The aim of this review was to highlight the effect and intracellular pathways of 1,25-D3 to modulate the spermatogenesis. The pivotal role of 1,25-D3 in male reproduction is reinforced by the presence of VDR and 1α-hydroxylase in reproductive tract. Also, the marked expression of VDR and the VD metabolizing enzymes in human testis, ejaculatory tract, and mature spermatozoa implicates the 1,25-D3 in spermatogenesis and maturation of human spermatozoa. Among genomic events, 1,25-D3 influences the expression of calcium binding protein and stimulates aromatase gene expression through a nongenomic activation of the membrane-bound VDR receptor involving the PKA pathway in the testis. Also, 1,25-D3 stimulates amino acid transport and exocytosis in testis by nongenomic events coupled to ionic currents triggered at plasma membrane. All together, the demonstration that 1,25-D3 regulates both Sertoli cell and sperm function may be useful for the study and development of new therapeutic strategies for the male reproductive disorders.