Effects of epidermal growth factor, phorbol ester, and retinoic acid on hormone synthesis and morphology in porcine thyroid follicles cultured in collagen gel.

Epidermal growth factor (EGF), phorbol esters (PEs), and retinoic acid (RA) inhibit differentiated functions of thyrocytes. In the present study the inhibitory effects of these growth-promoting factors on hormone synthesis were studied in thyroid follicles cultured in type-I collagen gel, and morphologic alteration by these factors was examined by light and electron microscopy (EM). Porcine open thyroid follicles obtained by treatment with 0.1% collagenase were embedded in collagen gel and cultured in Ham's F12 medium supplemented with 6H (insulin, hydrocortisone, somatostatin, transferrin, glycyl-his-lys, and thyrotropin) + 0.5% fetal bovine serum (FBS). After 1 week these open follicles developed to closed follicles, and the medium was changed to one containing 6H + 0.5% FBS + 0.1 microM sodium iodide (NaI). Some media were supplemented with either EGF, phorbol 12-myristate 13-acetate (PMA), or all-trans RA. The closed follicles retained ability for hormone synthesis for 2 weeks after the medium change in the presence of 6H + FBS + NaI. The amounts of T4 and T3 secreted into the culture medium from day 9 to day 12 after the medium change were 60% and 45% of those from day 0 to day 4, respectively. EGF reduced production of T4 and T3 by 61% and 69%, respectively; PMA, by 87% and 99%; and RA, by 55% and 44%. In the medium supplemented with 6H + 0.5% FBS, the follicles exhibited intact polarity. Apical surfaces with microvilli were oriented to the follicular lumen and tight junctions were on the apical side of cell-to-cell contacts. Desmosomes were found on both the apical and basal halves of the cell contacts.(ABSTRACT TRUNCATED AT 250 WORDS)