Bechtner G, Schopohl D, Rafferzeder M, Gärtner R, Welsch U, Stimulation of thyroid cell proliferation by epidermal growth factor is different from cell growth induced by thyrotropin or insulin-like growth factor I. Eur J Endocrinol 1996;134:639–48. ISSN 0804–4643
Isolated intact porcine thyroid follicles free of contaminating single cells were embedded in "Matrigel". which is a gel-forming basement membrane preparation containing mainly collagen type IV, laminin, heparan sulfate proteoglycans and entactin. Follicles were treated with different growth factors: thyrotropin (TSH), insulin-like growth factor I (IGF-I), epidermal growth factor (EGF) or transforming growth factor beta. Cell proliferation was quantified by counting cell numbers. Morphological studies were done by photodocumentation and analysis of histology by light and electron microscopy. The thyrocytes had the physiological polarity with follicular cell arrangement, microvilli at the apical membrane, desmosomes and tight junctions. The lumen contained colloid. Iodide organification (10.2 ± 2.1 vs 26.1 ± 5.8 pmol/106 cells; TSH 0.1 mU/ml) and release of thyroid hormones thyroxine, 1754 ± 207 vs 2890 ± 460 pg/106 cells; triiodothyronine. 164 ± 22 vs 412 ± 106 pg/106 cells; TSH, 1 mU/ml) were significantly stimulated by TSH. There was no basal growth rate in serum-free medium but proliferation was slightly stimulated with TSH (1 mU/ml;149 ± 19%) and in the same order of magnitude with IGF-I (10 ng/ml; 159 ± 23%) but without follicle neoformation. In contrast, EGF (1.0–5.0 ng/ml) induced thyrocyte proliferation dose dependently three- to sixfold. With EGF up to 2 ng/ml, buds of new follicles formed surrounding pre-existing follicles. With EGF higher than 3 ng/ml, typical papillary structures developed. Transforming growth factor beta inhibited this dedifferentiated growth. A migration of single cells into the gel was never observed. Thus, three-dimensional culture of isolated thyroid follicles in "Matrigel" provides a tool for investigating the regulation of follicular growth and neoformation close to the in vivo situation.
G Bechtner, Medizinische Klinik, Klinikum Innenstadt, Ludwig-Maximilians-Universität München, Ziemssenstraße 1, 80336 München, Germany