Receptor down regulation, peptide hormones

The concentration and afiinity of somatomedin receptors on intact cells and isolated membranes are subject to modulation by a variety of ctors. In common with many other peptide hormone receptors, SM-C/IGF-I receptors on cultured IM-9 lymphocytes are down-regulated by exposure of the cells to SM-C/IGF-I. Insulin and other related peptides are also capable of causing receptor loss, with a potency proportional to their ability to bind to the SM-C/IGF-I receptor (RII). In contrast, binding sites for MSA tracer (i.e., type-II sites) on chondrosarcoma chondrocytes are reported to be un-... 

Receptor down-regulation, internalization of a receptor induced by an excess of a peptide hormone, leading to disappearance of the receptor. This results in a temporary stimulation, followed by inhibition of the target cells. 

It should be pointed out, however, that not all hormones dissociate from their receptor in the pH 5.5 environment of the endosome [24], Some hormone-receptor complexes require much lower pH values for dissociation to occur. Although not a peptide hormone, the iron-transport protein transferrin is a peculiar example of this phenomenon and should be pointed out. In this case, at the neutral pH of the extracellular fluid transferrin containing bound iron binds to its cell surface receptor and is internalized. In the low pH environment of the endosome, iron becomes dissociated from transferrin, but transferrin remains bound to its receptor. The transferrin receptor, with bound transferrin, is then recycled to the cell surface. With iron no longer bound to the transferrin, the transferrin readily dissociates from its receptor at the neutral pH of the extracellular fluid [25,26]. This mechanism provides for an efficient continual uptake of iron into cells. Unlike transferrin, however, in those instances where peptide hormones have been documented not to be dissociated from their receptor in the endosome compartment, the hormone and receptor are delivered to the lysosomes via fusion of the endosomes with lyso-somes, where both hormone and receptor are degraded [24,27]. The continuous degradation of the receptor with each round of RME eventually leads to a decrease in the number of receptors on the cell surface, a phenomenon called down-regulation. 

Calcitonin is a peptide hormone produced by the C cells of the thyroid gland (in mammals). It acts on bone (inhibiting osteoclasis) to reduce the rate of bone turnover, and on the kidney to reduce reabsorption of calcium and phosphorus. It is obtained from natural sources (pork, salmon, eel), or S3mthesised. The t/ varies according to source t/ human is 10 min. Antibodies develop particularly to pork calcitonin and neutralise its effect synthetic salmon calcitonin (salcatonin) is therefore preferred for prolonged use loss of effect may also be due to down-regulation of receptors. Calcitonin is used (s.c., i.m. or intranasally) to control hypercalcaemia (rapid effect), Paget s disease of bone (relief of pain, and to relieve compression of nerves, e.g. auditory cranial), metastatic bone cancer pain, and postmenopausal osteoporosis. 

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