title: The effects of retinoic acid on the insulin-like growth factor axis in primary tissue culture from hyperparathyroidism.
abstract: BACKGROUND
  The importance of the IGF system in HPT has been previously demonstrated. Additionally, the role of vitamin A in HPT has been reported. Retinoic acid (RA), a derivative of vitamin A, is a ligand for the IGF II receptor (IGF2R). We have evaluated the interactions of RA with the IGF system in a primary parathyroid cell culture model.
  
  
  METHODS
  Primary cell cultures were prepared from nine patients. Following adhesion, the cells were transferred to serum-free medium and dosed once with growth factors +/- RA for 96 hours. Proliferation was assessed by measuring tritiated thymidine incorporation.
  
  
  RESULTS
  Compared with the control group (100%), both IGF I and II increased DNA synthesis significantly. Retinoic acid significantly reduced the basal DNA synthesis to 82.2% +/- 4.2% compared with control (P < 0.05). Retinoic acid x10(-5) M completely abrogated the proliferative actions of IGF II (70.2% +/- 9.7%, P < 0.05) but had no significant effect on the IGF I response (P > 0.05). To evaluate the role of IGF2R or IGFBPs in mediating the actions of RA, the IGF II analogs [Leu27]IGF II (10-20-fold reduced IGF I receptor affinity) and des(1-6) IGF II (lower IGFBP binding affinity) were used. The IGF II inhibitory effect of RA was enhanced in the presence of analogs [Leu27]IGF II (P = 0.052) but not with des(1-6)IGF II (P > 0.05), compared with wild-type IGF II.
  
  
  CONCLUSIONS
  These data implicate a novel antiproliferative role for RA in enhancing the pericellular clearance of IGF II via the IGF2R preventing ligand activation of the IGF I receptor. This may have broader implications for RA effects in other tumors.
authors: Division of Surgery, University of Bristol, Bristol Royal Infirmary, Marlborough Street, Bristol, United Kingdom, BS2 8HW. chriswong@tiscali.co.uk
authors: Chris K M
authors: CK
authors: Wong
authors: Teresa
authors: T
authors: Lai
authors: Jeffrey M P
authors: JM
authors: Holly
authors: Malcolm H
authors: MH
authors: Wheeler
authors: Claire E H
authors: CE
authors: Stewart
authors: John R
authors: JR
authors: Farndon