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Comparison of the effects of acute estrogen deficiency vs. lactation on calcium and bone metabolism. Acute estrogen deficiency (e.g., GnRH analog therapy) increases skeletal resorption and raises the blood calcium; in turn, PTH is suppressed and renal calcium losses are increased. During lactation, the combined effects of PTHrP (secreted by the breast) and estrogen deficiency increase skeletal resorption, reduce renal calcium losses, and raise the blood calcium, but calcium is directed into breast milk.

Model of intestinal calcium transport. Calcium enters the microvillus of the intestinal epithelial cell through TRPV6 (previously known as CaT1) calcium channel. Within the microvillus calcium is bound to calmodulin (CaM) which is itself bound to brush border myosin I (BBMI). BBMI may facilitate the movement of the calcium/CaM complex into the terminal web where the calcium is picked up by calbindin (CaBP) and transported through the cytoplasm in endocytic vesicles. At the basolateral membrane the calcium is pumped out of the cell by the Ca-ATPase (PMCA1b). 1,25(OH)2D enhances intestinal calcium transport by inducing TRPV6, CaBP, and PMCAb as well as increasing the amount of CaM bound to BBMI in the brush border.

A model of 1,25(OH)2D and calcium regulated keratinocyte differentiation. The G-protein coupled calcium receptor (CaSR) when activated by extracellular calcium activates Gα as described in the legend to figure 6. Gα stimulates PLC mediated hydrolysis of PIP2 to IP3 and DG. IP3 releases Cai from intracellular stores, and DG activates PKC. Depletion of intracellular calcium stores leads to influx of calcium across store operated calcium channels. PKC stimulation leads to activation of AP-1 transcription factors which along with calcium and 1,25(OH)2D activated transcription factors stimulate the expression of genes essential for the differentiation process. 1,25(OH)2D regulates this process by inducing CaSR and PLC as well as genes essential for cornified envelope formation such as involucrin and transglutaminase.

Schematic illustration contrasting calcium homeostasis in human pregnancy and lactation, as compared to normal. The thickness of arrows indicates a relative increase or decrease with respect to the normal and non-pregnant state. Although not illustrated, the serum (total) calcium is decreased during pregnancy, while the ionized calcium remains normal during both pregnancy and lactation.