The aim of the present study was to assess the effects of insulin-like grow
th factor I (IGF-I) upon the synthesis of 1,25-dihydroxyvitamin D-3 [1,25-(
OH)(2)D-3] by human placenta trophoblasts in culture. Cytotrophoblastic cel
ls obtained from normal term human placentae were cultured in Dulbecco's mo
dified Eagle's medium with HEPES and glucose (DMEM-HG) during 72 h and furt
her incubated in serum-free DMEM-F12 in the presence of IGF-I prior to the
addition of [H-3]-25-(OH)D-3 used as a precursor. The results showed that 2
h preincubation time with IGF-I was required for maximal production of [H-
3]-1,25-(OH)(2)D-3. Cultures in the presence of increasing concentrations o
f IGF-I (0-6.5 nmol/l), added 2 h before incubation with the labelled subst
rate, resulted in a dose-dependent response increment of [H-3]-1,25-(OH)(2)
D-3 production with a maximal conversion rate at the dose of 2.6 nmol/l. Hi
gher doses of IGF-I did not result in further stimulatory effects. Go-incub
ations in the presence of cycloheximide significantly (P < 0.0001) inhibite
d the IGF-I-mediated effects upon [H-3]-1,25(OH)(2)D-3 production. Identity
of putative [H-3]-1,25-(OH)(2)D-3 produced by human placenta was confirmed
by spectral and receptor binding analysis. These results demonstrate the a
bility of cultured human syncytiotrophoblast cells to convert 25-(OH)D-3 to
1,25-(OH)(2)D-3 and suggest a local protein-dependent regulatory effect of
IGF-I upon this biotransformation.