Molecular Human Reproduction, Vol. 5, No. 8, 771-776,
August 1999
© 1999 European Society of Human Reproduction and Embryology
Effects of IGF-I on 1,25-dihydroxyvitamin D3 synthesis by human placenta in culture
1 Departments of Reproductive Biology and 2 Physiology of Nutrition, Instituto Nacional de la Nutrición Salvador Zubirán, Vasco de Quiroga No 15, Col. Tlalpan, CP 14000, México DF, México, and 3 Unité CNRS UPR 1524, Endocrinologie, Métabolisme et Développement, Hôpital Saint Vincent de Paul, Paris, France
The aim of the present study was to assess the effects of insulin-like growth factor I (IGF-I) upon the synthesis of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] by human placenta trophoblasts in culture. Cytotrophoblastic cells obtained from normal term human placentae were cultured in Dulbecco's modified Eagle's medium with HEPES and glucose (DMEM-HG) during 72 h and further incubated in serum-free DMEM-F12 in the presence of IGF-I prior to the addition of [3H]-25-(OH)D3 used as a precursor. The results showed that 2 h preincubation time with IGF-I was required for maximal production of [3H]-1,25-(OH)2D3. Cultures in the presence of increasing concentrations of IGF-I (0–6.5 nmol/l), added 2 h before incubation with the labelled substrate, resulted in a dose-dependent response increment of [3H]-1,25-(OH)2D3 production with a maximal conversion rate at the dose of 2.6 nmol/l. Higher doses of IGF-I did not result in further stimulatory effects. Co-incubations in the presence of cycloheximide significantly (P < 0.0001) inhibited the IGF-I-mediated effects upon [3H]-1,25-(OH)2D3 production. Identity of putative [3H]-1,25-(OH)2D3 produced by human placenta was confirmed by spectral and receptor binding analysis. These results demonstrate the ability of cultured human syncytiotrophoblast cells to convert 25-(OH)D3 to 1,25-(OH)2D3 and suggest a local protein-dependent regulatory effect of IGF-I upon this biotransformation.
1,25-(OH)2D3/IGF-I/placenta/syncytiotrophoblasts
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