Selective estrogen receptor modulators inhibit the effects of insulin-like growth factors in hyperparathyroidism.
BACKGROUND
Primary hyperparathyroidism (HPT) predominantly affects perimenopausal women, leading to speculations that an estrogen imbalance may be liable. We have previously demonstrated the importance of the insulin-like growth factor (IGF) axis in HPT. Because the antiestrogen tamoxifen has been shown to modulate the IGF axis, we examined the interactions of selective estrogen receptor modulators (SERMs) and IGF in HPT. METHODS; Estrogen receptors were evaluated by Western immunoligand blotting. Sixteen parathyroid glands from 19 patients were included. After adhesion, the cells were treated with IGF (I or II) +/- estrogen +/- SERMs (tamoxifen, ICI 182,780) for 96 hours in serum-free media. Proliferation was assessed by measuring tritiated thymidine incorporation.


RESULTS
Both primary and secondary HPT express estrogen receptors alpha and beta. Primary and secondary HPT had comparable responses to SERMs, they were analyzed together. Compared with control (100%), IGFs (I and II) induced a significant increase in DNA synthesis. Estradiol at 10(-8) and 10(-7) mol/L (physiologic range) had no significant effects on IGF (I and II, P >.05). Both tamoxifen and ICI 182,780 inhibited basal DNA synthesis (P <.05) and abolished the effects of both IGF I and II (P <.05).


CONCLUSIONS
SERMs are capable of reducing basal and IGF-stimulated DNA synthesis. This reduction in proliferation has implications for cancer biology and therapeutic potential for SERMs in HPT.
Wong
Chris
C
Level 7, Division of Surgery, Bristol Royal Infirmary, Bristol BS2 8HW, UK.
Lai
Teresa
T
Hilly
Jeff M P
JM
Stewart
Claire E H
CE
Farndon
John R
JR
D000236:Adenoma; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010282:Parathyroid Neoplasms; D011869:Radioligand Assay; D011960:Receptors, Estrogen / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000378:metabolism / Q000494:pharmacology; D013629:Tamoxifen / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II