Growth regulation of normal thyroids and thyroid tumors in man

Our studies using thyrocyte membranes from different human thyroid tissues, monolayer cultures of human thyrocytes, and the permanant cell line FTC-133 demonstrate the stimulatory effect of TSH on metabolism, DNA synthesis, and cell growth in human thyrocytes. Up- and down-regulation of cAMP cell content fails to show direct effects on DNA synthesis and cell growth in primary thyrocyte cultures in man. Increased AC responsiveness to TSH in adenomatous human thyroid tissues, when compared to normal thyroids of the same patient (p less than 0.005), is thus of only questionable importance for thyroid tumor growth. The permanant cell line FTC-133 was established from differentiated follicular human thyroid cancer cells. FTC-133 cells proved to be of particular usefulness in assessing growth regulation of human thyroid tissue. These cells could be propagated in serum free medium, showed thyroglobulin immunoreactivity and EGF receptors, lacked any fibroblast contamination, and responded to TSH and local active growth factors such as EGF and IGF with a stimulated [3H]thymidine incorporation. The latter could be shown in primary cell cultures of normal and pathological human thyrocytes as well. Additional to the stimulatory effect of TSH and IGF on [3H]thymidine incorporation, these substances show an additive effect when incubated simultaneously. Locally active growth factors and endocrine growth stimulation by TSH therefore act synergistically on thyrocyte growth in human thyrocyte cultures. Whether the TSH effect on cell growth is related to its stimulation of AC remains as yet questionable.