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Calcium is involved in many physiologic processes. It is key to skeletal muscle and myocardial contraction, neurotransmission, and blood coagulation. In addition, it is the primary mineral in the bony skeleton. On the cellular level, its diverse functions include transmission of information into and between cells, regulation of plasma membrane potential, and exocytosis. Only over the last 20 years has its effect on skin been fully appreciated. Calcium regulates major functions in the epidermal keratinocytes including proliferation, differentiation, and cell–cell adhesion.1–6
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At least three regulatory hormones control the ionic calcium concentration in serum: (1) parathyroid hormone (PTH), (2) calcitonin, and (3) 1,25-dihydroxyvitamin D3 (1,25(OH)2D3).
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PTH is an 84-amino acid, single-chain polypeptide that is synthesized in the parathyroid glands. Under normal conditions, a decrease in the serum concentration of ionized calcium results in an increase in PTH production, whereas an increase in the serum concentration of ionized calcium results in a decrease in PTH production. In the kidney, PTH increases renal tubular reabsorption of calcium and increases renal clearance of phosphate. PTH also acts directly on the bone to increase the plasma calcium concentration. It does this acutely by mobilizing calcium from bone into the extracellular fluid. Osteocytes and osteoblasts are the presumed target cells for this effect. PTH also stimulates osteoclastic bone resorption, possibly by stimulating osteoblasts to release factors that activate osteoclasts. PTH together with a decreased plasma phosphate concentration stimulates 1α-hydroxylase activity in the kidney, causing an increase in the plasma concentration of 1,25(OH)2D3. 1,25(OH)2D3 increases intestinal absorption of calcium.
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Calcitonin is a 32-amino acid polypeptide that is produced by parafollicular or C cells of the thyroid gland. Calcium is the primary stimulant for calcitonin secretion. Calcitonin lowers the serum calcium concentration, primarily through osteoclast inhibition, but whether it plays a major role in serum calcium metabolism outside of the neonatal period in vivo is unclear.
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Vitamin D3, or cholecalciferol, is a secosteroid (steroid with a “broken” ring) formed by the opening of the β ring of 7-dehydrocholesterol. In humans, this formation occurs in the basal layer of the epidermis. First, there is an ultraviolet B-mediated conversion of 7-dehydrocholesterol to previtamin D3. Previtamin D3 then undergoes thermal isomerization to form vitamin D3. To become biologically active, vitamin D3 must first be hydroxylated at carbon position 25 in the liver and then at carbon position 1α by the enzyme 1α-hydroxylase in the kidney. 1α-hydroxylase is tightly regulated. PTH and ...