[Parathyroid hormone receptors: from cloning to physiological, physiopathological and clinical implications].
It has long been known that parathyroid hormone (PTH) exerts its effects on target tissues via its binding to a membrane receptor. Recently, several types of PTH receptors have been identified. The first receptor which has been cloned and well characterized is "PTH/PTHrP receptor-1". It is activated not only by PTH, but also by PTH-related peptide (PTHrP), via a signal transduction system involving G-proteins, adenylate cyclase and phospholipase C. It is expressed in many tissues, in addition to kidney and bone. The results of recent studies are suggestive of the existence of additional PTH receptors. One or several receptors are probably expressed in the keratinocyte and the glomerular podocyte which are not identical with PTH/ PTHrP receptor-1. A third receptor, which has been cloned recently and called "PTH2 receptor", recognizes solely PTH. It is expressed in brain, pancreas, testis and placenta. Its function is unknown. There is also evidence for a fourth receptor, called "C-PTH receptor", recognizing C-terminal PTH fragments which are generally considered to be biologically inactive. The regulation of these receptors is subject to intensive research. Down-regulation of PTH/PTHrP receptor-1 mRNA expression could explain the well-known resistance to the action of PTH in chronic renal failure. In contrast, the receptor mRNA is up-regulated in vitamin D deficiency, despite a similar tissue resistance to PTH. A mutation of PTH/PTHrP receptor-1 causes Jansen-type metaphyseal chondrodysplasia. However, no alteration of the PTH/PTHrP receptor-1 gene structure has been found in type 1b pseudohypoparathyroidism.
Mannstadt
M
M
Drüeke
T B
TB
D000818:Animals; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D011547:Pseudohypoparathyroidism / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000235:genetics / Q000502:physiology*
D012333:RNA, Messenger; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone