Regulation of serum calcium or 1,25 dihydroxyvitamin D3, and
calcitonin is a hormone secreted by the
thyroid gland when the plasma ionized calcium level is high or rising.The diagram does not show the extremely small amounts of calcium that move into and out of the cells of the body, nor does it indicate the calcium that is bound to the extracellular proteins (in particular the plasma proteins) or to plasma phosphate. Parathyroid hormone regulates
serum calcium through its effects on bone, kidney, and the intestine: In bone, PTH enhances the release of calcium from the large reservoir contained in the bones.
Bone resorption is the normal destruction of bone by
osteoclasts, which are indirectly stimulated by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to
osteoblasts, the cells responsible for creating bone. Binding stimulates osteoblasts to increase their expression of RANKL and inhibits their secretion of
osteoprotegerin (OPG). Free OPG competitively binds to
RANKL as a
decoy receptor, preventing RANKL from interacting with
RANK, a receptor for RANKL. The binding of RANKL to RANK (facilitated by the decreased amount of OPG available for binding the excess RANKL) stimulates osteoclast precursors, which are of a
monocyte lineage, to fuse. The resulting multinucleated cells are osteoclasts, which ultimately mediate
bone resorption. Estrogen also regulates this pathway through its effects on PTH. Estrogen suppresses T cell TNF production by regulating T cell differentiation and activity in the bone marrow, thymus, and peripheral lymphoid organs. In the bone marrow, estrogen downregulates the proliferation of hematopoietic stem cells through an IL-7 dependent mechanism. In the kidney, around 250 mmol of calcium ions are filtered into the
glomerular filtrate per day. Most of this (245 mmol/d) is reabsorbed from the tubular fluid, leaving about 5 mmol/d to be excreted in the urine. This reabsorption occurs throughout the tubule (most, 60–70%, of it in the
proximal tubule), except in the thin segment of the
loop of Henle. Circulating parathyroid hormone only influences the reabsorption that occurs in the
distal tubules and the
renal collecting ducts A third important effect of PTH on the kidney is its stimulation of the conversion of
25-hydroxy vitamin D into
1,25-dihydroxy vitamin D (
calcitriol), which is released into the circulation. This latter form of vitamin D is the active hormone which stimulates calcium uptake from the intestine. Via the kidney, PTH enhances the absorption of calcium in the
intestine by increasing the production of activated
vitamin D. Vitamin D activation occurs in the kidney. PTH up-regulates
25-hydroxyvitamin D3 1-alpha-hydroxylase, the enzyme responsible for 1-alpha
hydroxylation of
25-hydroxy vitamin D, converting vitamin D to its active form (1,25-dihydroxy vitamin D). This activated form of vitamin D increases the absorption of calcium (as Ca2+ ions) by the intestine via
calbindin. PTH was one of the first hormones to be shown to use the G-protein
adenylyl cyclase second messenger system.
Regulation of serum phosphate PTH reduces the reabsorption of
phosphate from the
proximal tubule of the kidney, which means more phosphate is excreted through the urine. However, PTH enhances the uptake of phosphate from the intestine and bones into the blood. In the bone, slightly more calcium than phosphate is released from the breakdown of bone. In the intestines, absorption of both calcium and phosphate is mediated by an increase in activated vitamin D. The absorption of phosphate is not as dependent on vitamin D as is that of calcium. The result of PTH release is a small net drop in the serum concentration of phosphate.
Vitamin D synthesis PTH upregulates the activity of
1-α-hydroxylase enzyme, which converts 25-hydroxycholecalciferol, the major circulating form of inactive vitamin D, into 1,25-dihydroxycholecalciferol, the active form of vitamin D, in the kidney.
Interactive pathway map == Regulation of PTH secretion ==