S. Pellerin et al., Regulation of the three-dimensional organization of thyroid epithelial cells into follicle structures by the matricellular protein, thrombospondin-1, ENDOCRINOL, 140(3), 1999, pp. 1094-1103
Thyroid epithelial cells in primary culture have the capacity to organize i
nto thyroid-specific three-dimensional structures, the follicles, in respon
se to TSH, We studied whether thrombospondin 1 (TSP1), which represents, be
sides thyroglobulin, the main protein secreted by thyroid cells, could play
a role in the process of folliculogenesis.
TSH promoted follicle formation and inhibited TSP1 production. On the contr
ary, the phorbol ester, 12-O-tetradecanoyl-phorbol 13-acetate (1-100 nM) pr
evented TSH-induced follicle formation and strongly increased the synthesis
of TSP1. Activation of TSP1 synthesis was dependent upon messenger RNA syn
thesis. Transforming growth factor-beta, like 12-O-tetradecanoyl-phorbol 13
-acetate, increased TSP1 synthesis and prevented TSH-induced follicle forma
tion. Thus, signaling molecules that depressed or conversely activated TSP1
production, respectively promoted or prevented thyroid folliculogenesis.
TSP1, purified from platelets, was devoid of effect on cell substratum atta
chment, but exerted a concentration-dependent inhibition of the TSH-activat
ed reconstitution of thyroid follicles (half-inhibition at 40 mu g/ml). TSP
1 exhibited the same effect when added to thyroid cell aggregates represent
ing primitive follicle structures.
Our data suggest that the control of thyroid follicle formation may operate
at least in part through regulation of the production of the matricellular
protein TSP1, which acts as a negative modulator of the cell-cell adhesion
process involved in thyroid follicle morphogenesis.