STIMULATION OF THYROID-CELL PROLIFERATION BY EPIDERMAL GROWTH-FACTOR IS DIFFERENT FROM CELL-GROWTH INDUCED BY THYROTROPIN OR INSULIN-LIKE GROWTH-FACTOR-I

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 TV, laminin, hepa ran sulfate proteoglycans and entactin. Follicles were treated with di fferent 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. Mor phological studies were done by photodocumentation and analysis of his tology by light and electron microscopy. The thyrocytes had the physio logical polarity with follicular cell arrangement, microvilli at the a pical membrane, desmosomes and tight junctions. The lumen contained co lloid. Iodide organification (10.2 +/- 2.1 vs 26.1 +/- 5.8 pmol/10(6) cells; TSH 0.1 mU/ml) and release of thyroid hormones (thyroxine, 1754 +/- 207 vs 2890 +/- 460 pg/10(6) cells; triiodothyronine, 164 +/- 22 vs 412 +/- 106 pg/10(6) cells; TSH, 1 mU/ml) were significantly stimul ated by TSH. There was no basal growth rate in serum-free medium but p roliferation was slightly stimulated with TSH (1 mU/ml;149 +/- 19%) an d in the same order of magnitude with TGF-I (10 ng/ml;159 +/- 23%) but without follicle neoformation. In contrast, EGF (1.0-5.0 ng/ml) induc ed thyrocyte proliferation dose dependently three- to sixfold. With EG F 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 dedifferent iated growth. A migration of single cells into the gel was never obser ved. Thus, three-dimensional culture of isolated thyroid follicles in ''Matrigel'' provides a tool for investigating the regulation of folli cular growth and neoformation close to the in vivo situation.