1,25-hydroxyvitamin D3 receptors (VDR) are present on rat granulosa cells and on human ovarian cancer cells, however little is known about 1,25-hydroxyvitamin D3 (1,25-(OH)2D3) function in the ovary. Vitamin D deficient rats have reduced fertility, and VDR null mutant mice demonstrate impaired folliculogenesis. Vitamin D metabolites have been detected in follicular fluid.
The aim of this study was to investigate the effect of a range of concentrations of 1,25-(OH)2D3 (2pM-20nM) on luteinised granulosa cells from IVF collections, or pooled unstimulated cells from small follicles. Cells were plated at concentration of 5x105 per well, and cultured in McCoys 5A modified medium. In the luteinised cells, 1,25-(OH)2D3 suppressed the production of oestradiol (E2) in a dose-responsive manner over 48 to 96 hours: median inhibition was 25% (range 0-70%). The lowest effective concentration was 20pM. LH-stimulated (5-10ng/ml) production of E2 was also inhibited: median inhibition 35% (range 5-50%). The production of progesterone (P) increased or was unchanged. In contrast, the effects on granulosa cells from small (<10mm) unstimulated follicles were variable. Vitamin D had little or no effect on baseline steroid production, but enhanced gonadotrophin stimulated P and E2 production.
In summary, 1,25-(OH)2D3 inhibited both basal and LH mediated E2 production by luteinised granulosa cells. In granulosa cells from small follicles, gonadotrophin-mediated steroidogenesis was enhanced. In conclusion, 1,25-(OH)2D3 may have a role in modulating folliculogenesis.