In view of new findings since the last International Workshop on the Management of Asymptomatic PHPT, guidelines for management have been revised. The revised guidelines include: 1) recommendations for more extensive evaluation of the skeletal and renal systems; 2) skeletal and/or renal involvement as determined by further evaluation to become part of the guidelines for surgery; and 3) more specific guidelines for monitoring those who do not meet guidelines for parathyroid surgery. These guidelines should help endocrinologists and surgeons caring for patients with PHPT. A blueprint for future research is proposed to foster additional investigation into issues that remain uncertain or controversial.
The complementary DNA encoding a 585-amino acid parathyroid hormone-parathyroid hormone-related peptide (PTH-PTHrP) receptor with seven potential membrane-spanning domains was cloned by COS-7 expression using an opossum kidney cell complementary DNA (cDNA) library. The expressed receptor binds PTH and PTHrP with equal affinity, and both ligands equivalently stimulate adenylate cyclase. Striking homology with the calcitonin receptor and lack of homology with other G protein-linked receptors indicate that receptors for these calcium-regulating hormones are related and represent a new family.
Consensus was achieved by a group meeting. Statements were prepared and reviewed by all authors who represented the Planning Committee and the participating professional societies.
Cell signaling mediated by the G protein-coupled parathyroid hormone receptor type 1 (PTHR) is fundamental to bone and kidney physiology. It has been unclear how the two ligand systems-PTH, endocrine and homeostatic, and PTH-related peptide (PTHrP), paracrine-can effectively operate with only one receptor and trigger different durations of the cAMP responses. Here we analyze the ligand response by measuring the kinetics of activation and deactivation for each individual reaction step along the PTHR signaling cascade. We found that during the time frame of G protein coupling and cAMP production, PTHrP 1-36 action was restricted to the cell surface, whereas PTH 1-34 had moved to internalized compartments where it remained associated with the PTHR and Gα s , potentially as a persistent and active ternary complex. Such marked differences suggest a mechanism by which PTH and PTHrP induce differential responses, and these results indicate that the central tenet that cAMP production originates exclusively at the cell membrane must be revised.Seminal studies during the past decades established that signaling cascades mediated by a G protein-coupled receptor (GPCR) initially proceed through a succession of biochemical events that take place at the cell membrane and result in the induction and propagation of second messenger molecules 1-4 (Fig. 1a). These events begin with the binding of an 'agonist' ligand (L) to an inactive-state receptor (R), which causes the receptor to switch to an active-state conformation (R*). The activated receptor then interacts with heterotrimeric G proteins (G, or Gαβγ) to form a transient L-R*-G complex, which exhibits higher affinity for the agonist ligand than does the initial L-R state. The interaction process further involves a conformational change-induced exchange of GDP for GTP on Gα with concomitant release of the activated, GTP-bound Gα (along with Gβγ) from the L-R complex, and the
This document not only provides a summary of our current knowledge but also places recent advances in its management into a context that should enhance future advances in our understanding of hypoparathyroidism.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.