Human placental production of 1 alpha,25-dihydroxyvitamin D3: biochemical characterization and production in normal subjects and patients with pseudohypoparathyroidism.

Biochemical characterization of placental 25-hydroxyvitamin D3-1 alpha-hydroxylase was performed in placentas from eight normal women. Production of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] was linear with time; the mean production rate was 282 +/- 74 (+/- SE) pg/mg protein X h. Only the fetally derived trophoblasts had significant 1 alpha-hydroxylase activity, and this was located solely in mitochondria. Kinetic analysis of 1 alpha-hydroxylation in isolated mitochondria from normal placentas disclosed a Km for 25-hydroxyvitamin D3 of 0.57 microM. To assess whether placentas from women with disorders of vitamin D metabolism could also produce 1,25-(OH)2D3, we measured the placental production rates of 1,25-(OH)2D3 in three women with PTH-resistant hypoparathyroidism (pseudohypoparathyroidism) during four separate pregnancies. Their mean production rate of 1,25-(OH)2D3 was 353 +/- 184 pg/mg protein X h, a value not significantly different from that of normal placentas. Therefore, placental production of 1,25-(OH)2D3 may provide a significant contribution to the circulating concentration of 1,25-(OH)2D3. In women with PTH-resistant hypoparathyroidism, in whom the renal capacity to synthesize 1,25-(OH)2D3 is impaired, placental production of 1,25-(OH)2D3 is not compromised.