Parathyroid hormone receptor, signal

Parathyroid hormone (PTH) regulates calcium levels in blood and bone remodeling. The activation domain of that 84-amino acid polypeptide locates around the N-terminal (1-34 amino acids). Parathyroid hormone receptor is a typical G-protein coupled receptor, which is coupled to both adenyl cyclase/cAMP and PLCy/IP3/cytosolic Ca2+ intracellular signaling pathways. In order to identify the structural elements involved in the peptide hormone binding and signal initiation, Chorev et al. employed a photoaffinity scanning approach. The N-terminal amino acids were successively deleted or modified and the new N-terminus was replaced for photoreactive Bpa. The most active peptide ana-... 

The mechanism of G a disease may resnlt from insnfficient parathyroid hormone-related peptide signaling by the parathyroid hormone receptor 1 (PTHRl) in chondrocytes. This deficiency may inhibit the differentiation of chondrocytes within the endochondral growth plate (88,89). A variety of parathyroid hormone abnormalities can result. 

Most GPCRs interact with and activate more than one G-protein subfamily, e.g., with Gs plus Gq/n (histamine H2, parathyroid hormone and calcitonin recqrtors), Gs plus G (luteinising hormone receptor, 32-adrenoceptor) or Gq/11 plus G12/13 (thromboxane A2, angiotensin ATb endothelin ETA receptors). Some receptors show even broader G-protein coupling, e.g., to Gi, Gq/n plus Gi n ( protease-activated receptors, lysophosphatidate and sphingosine-1-phosphate receptors) or even to all four G-protein subfamilies (thyrotropin receptor). This multiple coupling results in multiple signaling via different pathways and in a concerted reaction of the cell to the stimulus. 

Such observations have led to the idea that depression may be a pseudomonoamine deficiency due to a deficiency in signal transduction from the monoamine neurotransmitter to its postsynaptic neuron in the presence of normal amounts of neurotransmitter and receptor. If there is a deficiency in the molecular events that cascade from receptor occupancy by neurotransmitter, it could lead to a deficient cellular response and thus be a form of pseudomonoamine deficiency (i.e., the receptor and the neurotransmitter are normal, but the transduction of the signal from neurotransmitter to its receptor is somehow flawed). Such a deficiency in molecular functioning has been described for certain endocrine diseases such as hypoparathyroidism (parathyroid hormone deficiency), pseudohypoparathyroidism (parathyroid receptors deficient but parathyroid hormone levels normal), and pseudo-pseudohypoparathyroidism (signal transduction deficiency leading to hypoparathyroid clinical state despite normal levels of hormone and receptor). 

Biochemical mechanism Elevated parathyroid hormone level acts by binding its 7-helix plasma membrane receptor to activate the adenylate cyclase/protein kinase A signaling system. 

Peptide-hormones like hypothalamus-pituitary, gastrointestinal, parathyroid, neurohormones, Gfs related peptide-hormones cannot penetrate the plasma membrane and their receptors are located on the cell surface and the signal transport to the nucleus is becoming via a second messenger. The main hormone action seems to be DNA synthesis whereas other including mediation of neurotransmission, enzyme synthesis, regulation and synthesis of structural proteins are responsible for the specific characteristics of differentiated cell. 

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