PARATHYROID-HORMONE - FROM CLONING TO PHY SIOLOGICAL, PATHOPHYSIOLOGICAL AND CLINICAL IMPLICATIONS

It has long been known that parathyroid hormone (PTH) exerts its effec ts on target tissues via its binding to a membrane receptor. Recently, several types of PTH receptors have been identified, The first recept or which has been cloned and well characterized is <<PTH/PTHrP recepto r-1>>. It is activated not only by PTH, but also by PTH-related peptid e (PTHrP), via a signal transduction system involving G-proteins, aden ylate cyclase and phospholipase C. It is expressed in many tissues, in addition to kidney and bone. The results of recent studies are sugges tive of the existence of additional PTH receptors. One or several rece ptors are probably expressed in the keratinocyle and the glomerular po docyte which are not identical with PTH/PTHrP receptor-1. A third rece ptor, which has been cloned recently and called <<PTH2 receptor>>, rec ognizes solely PTH. It is expressed in brain, pancreas, testis and pla centa. Its function is unknown. There is also evidence for a fourth re ceptor, called <<C-PTH receptor>>, recognizing C-terminal PTH fragment s which are generally considered to be biologically inactive. The regu lation of these receptors is subject to intensive research. Down-regul ation of PTH/PTHrP receptor-1 mRNA expression could explain the well-k nown resistance to the action of PTH in chronic renal failure. In cont rast, the receptor mRNA is up-regulated in vitamin D deficiency, despi te a similar tissue resistance to PTH. A mutation of PTH/PTHrP recepto r-1 causes Jansen-type metaphyseal chondrodysplasia. However, no alter ation of the PTH/PTHrP receptor-1 gene structure has been found in typ e 1b pseudohypoparathyrodism.