Gc. Priestley et al., SKIN FIBROBLAST ACTIVITY IN PRETIBIAL MYXEDEMA AND THE EFFECT OF OCTREOTIDE (SANDOSTATIN(R)) IN-VITRO, British journal of dermatology, 131(1), 1994, pp. 52-56
The accumulation of glycosaminoglycans in the skin in pretibial myxoed
ema appears to be a response by local fibroblasts to a stimulating fac
tor in the patient's serum, but the identity of the factor, its abilit
y to stimulate skin fibroblasts as opposed to cultured thyroid cells,
and the specificity of its effect to pretibial skin fibroblasts, are a
ll controversial. We have studied fibroblasts cultured from the lesion
al skin of two women with pretibial myxoedema, and compared their prol
iferation and secretion of glycosaminoglycans with those of fibroblast
s from the patients' forearms and from the forearm skin of two normal
subjects. We found that in the presence of the patients' sera all six
lines of fibroblasts secreted more glycosaminoglycans [205 +/- 21% (SD
)] than with normal human sera (147 +/- 19%), or fetal calf serum (100
%). Fibroblast proliferation showed the same pattern of differences: p
atients' sera 142 +/- 22%; normal human sera 116 +/- 9%, and fetal cal
f serum 100%. These experiments confirm the presence of a serum factor
in pretibial myxoedema which is capable of stimulating the activity o
f skin fibroblasts in vitro, and show that its effects are not restric
ted to fibroblasts from pretibial skin or to those grown from the skin
of the patients. Proliferation of normal fibroblasts cultured in medi
um supplemented with fetal calf serum was reduced by Sandostatin(R) (o
ctreotide), but it failed to inhibit their secretion of glycosaminogly
cans. In contrast, secretion of glycosaminoglycans by a patient's pret
ibial skin fibroblasts was almost completely inhibited by 1 mM minoxid
il. In the presence of patients' sera Sandostatin(R) (0.1-10 mu g/ml)
reduced secretion of glycosaminoglycans by about 50%. Our data support
the use of Sandostatin(R) in pretibial myxoedema, and suggest that it
may suppress fibroblast glycosaminoglycan secretion within the skin v
ia depletion of insulin-like growth factor or the blocking of its effe
ct.