ROLE OF EXTRACELLULAR CALCIUM IN THE REGULATION OF 1,25-DIHYDROXYVITAMIN D-3 FORMATION IN CULTURED HUMAN KERATINOCYTES

Cultured normal human keratinocytes (NHK) provide a useful experimenta l model for studies of processes occuring during terminal differentiat ion, since the extent of keratinocyte maturation can be manipulated ex perimentally by modulation of extracellular calcium concentration. Whe n NHK are maintained in low calcium (0.06 mM) medium they proliferate but do not stratify. Raising the level of calcium to 1-2 mM results wi thin a few hours in induction of keratinocyte differentiation. Results of the present study show that formation of 1,25-(OH)(2)D-3 is higher in NHK grown at 0.06 mM than in NHK grown at 1.6 mM calcium concentra tion. After 2 h exposure of low calcium cultures to 1.6 mM calcium the 1,25-(OH)(2)D-3 production starts to decrease. On the other hand, exp osure of cells cultured in 1.6 mM calcium medium to 0.06 mM calcium co ncentration induced already within 4 h an increase in 1,25-(OH)(2)D-3 formation which was not accompanied by a decrease in cornified envelop e formation. Thereby, the present study demonstrated that calcium can regulate 1,25-(OH)(2)D-3 formation independently of changes in keratin ocyte differentiation.