Endocrinol Metab.  2011 Mar;26(1):25-32. 10.3803/EnM.2011.26.1.25.

Molecular Understanding and Assessment of Hypoparathyroidism

• Yi HS
• Choi B
• Lee S

• KMID: 2169120
• DOI: http://doi.org/10.3803/EnM.2011.26.1.25

Abstract

No abstract available.

MeSH Terms

Hypoparathyroidism

Figure

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  Fig. 1. Calcium Homeostasis. In response to declines in serum calcium, the parathyroid glands secrete parathyroid hormone (PTH). PTH stimulates the release of Ca2+ from bone, increasing bone resorption. In the kidney, PTH stimulates tubular reabsorption of Ca2+ and synthesis of calcitriol (1, 25[OH]2D3, the biologically active form of vitamin D) in the kidney. The main physiological function of calcitriol is to increase intestinal Ca2+ absorption. Therefore, all effects of PTH act to directly or indirectly increase the calcium concentration in the extracellular fluids.

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  Fig. 2. Primary sequence of human PTH and organization of its domain. The pre (signal sequence), pro (black box), and mature regions (boxed) of PTH are labeled. The arrowheads point toward the Cys residue (C18) that is replaced by Arg (R) and Ser residue (S23) that is replaced by Pro (P).

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  Fig. 3. The structure of the CaSR. A model of the dimeric form of the extracellular calcium-sensing receptor (CaSR), with each of the two individual receptor molecules of the dimer pair shown in red and blue. The bi-lobed, venus-flytrap domain of the CaR is modeled on the known crystal structure of the metabotropic glutamate receptor type 1. The approximate locations of the five putative protein kinase C phosphorylation sites are indicated by yellow triangles. The grey circles indicate individual cysteine residues that comprise the cysteine-rich domain (From Hofer et al. Nat Rev Molec Cell Biol 4:530–538, 2003[25]).

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  Fig. 4. Extracellular calcium sensing and signaling. Numerous agonists converge on the extracellular calcium-sensing receptor (CaSR) to activate a complex network of intracellular signal-transduction cascades. Please refer to the text for further details. AA, arachidonic acid; AC, adenylate cyclase; cAMP, cyclic AMP; cPLA2, cytosolic phospholipase A2; DAG, diacylglycerol; ERK, extracellular-sig-nal-regulated kinase; G i and G q, subunits of the i- and q-type heterotrimeric G proteins, respectively; Ins(1,4,5)P3, inositol-1,4,5-trisphosphate; Ins(1,4,5)P3 R, inositol-1,4,5-trisphosphate receptor; JNK, Jun amino-terminal kinase; MAPK, mitogen-activated protein kinase; MEK, MAPK kinase; PI4K, phosphatidylinosi-tol 4-kinase; PKC, protein kinase C; PLC, phospholipase C; PtdIns(4,5)P2, phosha-tidylinositol-4,5-bisphosphate (From Hofer et al. Nat Rev Molec Cell Biol4:530–538, 2003[25]).

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  Fig. 5. GCMB gene structure and previously reported mutations.

Reference

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