Y. Shakhov et al., REDUCED SENSITIVITY OF CULTURED SKIN FIBROBLASTS FROM FAMILIAL HYPERCHOLESTEROLEMIC PATIENTS TO GLUCOCORTICOIDS, Life sciences, 53(21), 1993, pp. 1617-1624
Cultured human skin fibroblasts, obtained from patients with homozygou
s familial hypercholesterolemia (FH), exhibited cholesterol synthesis
that was 2.5-3-fold more intensive than in cells from healthy donors (
normal cells). The study of the glucocorticoid [H-3]-dexamethasone spe
cific binding (glucocorticoid receptors, GcR) to the cells showed redu
ced number of binding sites (8 x 10(3) vs 120 x 10(3) binding sites/ce
ll) and reduced Kd value (5.6 +/- 0.7 vs 10.1 +/- 2.1 nM) in FH-fibrob
lasts when compared with normal fibroblasts. The inhibition by 1 x 10(
-8) and 1 x 10(-6) M dexamethasone of cholesterol synthesis was less m
arked in FH-cells (29.1 +/- 2.8 and 35.9 +/- 1.2%) as compared with no
rmal cells (53.3 +/- 1.0% and 60.4 +/- 9.6, respectively). This findin
gs indicate that the sensitivity of FH-fibroblasts to glucocorticoids
is reduced. They also suggest that reduced number of GcR found in FH-f
ibroblasts reflects the cellular adaptation to cholesterol deficiency
resulted from the absence of LDL-receptors.