PMID- 12476790
OWN - NLM
STAT- MEDLINE
DCOM- 20030128
LR  - 20181130
IS  - 1568-0088 (Print)
IS  - 1568-0088 (Linking)
VI  - 2
IP  - 2
DP  - 2002 Jul
TI  - Molecular basis of hyperparathyroidism and potential targets for drug 
      development.
PG  - 167-79
AB  - Our appreciation of the molecular pathogenesis of primary hyperparathyroidism 
      (HPT) has seen great advances over the past decade. This improved understanding 
      may well lead to the development of new treatment options that are specifically 
      targeted to defective pathways. This review summarizes recent advances in the 
      molecular basis of HPT and associated endocrinopathies, and discusses the 
      potential for these and future findings to provide targets for alternative 
      approaches to therapy. The only proven contributors to common sporadic HPT, by 
      virtue of clonal genetic abnormalities, are the cyclin D1 and MEN1 genes. Cyclin 
      D1 is an oncogene that encodes a key regulator of the cell cycle, while MEN1 is a 
      tumor suppressor gene that has also been implicated in familial multiple 
      endocrine neoplasia type 1 (MEN1), in which primary HPT is common. In addition, 
      other key parathyroid regulatory pathways may play a role in HPT pathogenesis. 
      1,25 (OH)2-vitamin D. Ca2+ and phosphate are regarded as principal regulators of 
      parathyroid cell proliferation and PTH secretion. Therefore, prime candidate 
      targets include the Ca2+ sensing receptor (CASR) gene, the vitamin D receptor 
      (VDR) gene, a putative phosphate receptor gene, their cognate gene products, and 
      other genes or proteins involved in their respective biochemical pathways. 
      Attempts to identify new therapies based specifically on the defective pathways 
      in HPT could complement or eventually supplant traditional approaches.
FAU - Krebs, L J
AU  - Krebs LJ
AD  - Center for Molecular Medicine, University of Connecticut Health Center, 263 
      Farmington Avenue, Farmington, CT 06030-3101, USA. Krebs@up.uchc.edu
FAU - Arnold, A
AU  - Arnold A
LA  - eng
GR  - 5K16-DE00157/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United Arab Emirates
TA  - Curr Drug Targets Immune Endocr Metabol Disord
JT  - Current drug targets. Immune, endocrine and metabolic disorders
JID - 101121150
RN  - 0 (Parathyroid Hormone)
RN  - 0 (Phosphates)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Receptors, Calcium-Sensing)
RN  - 0 (Receptors, Cell Surface)
RN  - 136601-57-5 (Cyclin D1)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Cyclin D1/genetics
MH  - Genes, Tumor Suppressor
MH  - Genes, bcl-1
MH  - Humans
MH  - Hyperparathyroidism/*drug therapy/*genetics
MH  - Multiple Endocrine Neoplasia Type 1/genetics
MH  - Parathyroid Hormone/metabolism
MH  - Phosphates/metabolism
MH  - Receptors, Calcitriol/genetics/physiology
MH  - Receptors, Calcium-Sensing
MH  - Receptors, Cell Surface/genetics/physiology
RF  - 111
EDAT- 2002/12/13 04:00
MHDA- 2003/01/29 04:00
CRDT- 2002/12/13 04:00
PHST- 2002/12/13 04:00 [pubmed]
PHST- 2003/01/29 04:00 [medline]
PHST- 2002/12/13 04:00 [entrez]
PST - ppublish
SO  - Curr Drug Targets Immune Endocr Metabol Disord. 2002 Jul;2(2):167-79.