The relationship of estrogen administration and pregnancy to vitamin D metabolism and Ca homeostasis was examined in two young women with pseudohypoparathyroidism. Estrogen, which is believed to inhibit PTH-mediated bone resorption, caused a consistent dose-related reversible reduction of serum Ca in these patients. This finding supports the concept that PTH-mediated bone resorption may contribute to the maintenance of serum Ca in normocalcemic pseudohypoparathyroidism. Paradoxically, these two patients remained normocalcemic throughout pregnancy, a high estrogen state. They were studied during four pregnancies, and each time a similar pattern emerged. Despite a primary derangement of the renal 1 alpha-hydroxylase, serum 1,25-dihydrovitamin D [1,25-(OH)2D] concentration increased 2- to 3-fold, while the serum PTH level was nearly halved during pregnancy. After delivery, serum Ca and 1,25-(OH)2D decreased, and serum PTH rose appropriately. Placental synthesis of 1,25-(OH)2D may have contributed to the maintenance of normocalcemia in these patients.
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