Endocrine Abstracts

Vascular endothelial growth factors (VEGFs) support angiogenesis and thus tissue growth. They are synthesised and secreted by several cell types but their actions are normally limited to endothelial cells which express VEGF receptors (VEGFRs). Using qRT-PCR and Western blotting we found that normal human thyroid follicular cells also express VEGFRs (VEGFR1-3, neuropilin1 and 2). We have examined the regulation of the expression of VEGFs and PlGFs in the cells. Cells were fully functional and trapped and organified ¹²⁵I. VEGFA and PlGFs were assayed by ELISA of serum-free, cell-conditioned medium. Primary cultures of human thyroid follicular cells secreted 5–10 ng VEGF per 10⁶ cells per day. This was considerably higher than the M61 thyroid endothelial cell line (2–4 ng per 10⁶ cells per day). TSH stimulated thyroid cell function but had no significant effects on VEGFA production in the functional preparations examined. PlGF production (∼5 ng per 10⁶ cells per day) was also high in functional cells and TSH dose-dependently increased PlGF production 2-fold. This effect was mimicked by forskolin suggesting a cAMP-mediated effect. Mitogenic growth factors (EGF, FGF) decreased cell function, had no effects on VEGF production but significantly decreased PlGF production. TNF alpha and TGF beta inhibited growth and ¹²⁵I uptake, and also significantly decreased PlGF production but had no effect on VEGF production. PKC activation with TPA also decreased PlGF production. We conclude that VEGFs and PlGFs may be autocrine factors for thyroid cells. VEGF production is constitutive whereas PlGF production is correlated with increased thyroid cell function. VEGF and PlGF are known to form heterodimers which can deplete functional VEGF homodimers. The increased expression of PlGF by TSH may thus decrease the autocrine effects of VEGFallowing greater expression of differentiated functions. Growth factors, by decreasing thyroidal PlGF production, may promote VEGF homodimer formation and angiogenesis.