Regulation of Growth and Differentiation in Follicle Cells

Abstract

Hypertrophy and hyperplasia follow chronic TSH stimulation in vivo. An early study by Matovinovic and Vickery1 showed that the total number of cells in guinea pig thyroid glands was increased 2.5 times following 14 daily injections of TSH. Another study showed that the volume of the nucleus was increased threefold in guinea pigs within 2h of an injection of TSH although mitotic activity was not increased until the third day.2,3 Data from rats suggest that in adults there is a very slow turnover of the thyroid cell population. Growth of endothelial and mesenchymal cells was observed to accompany that of thyroid follicular cells when rats were given goitrogens.4 In man there are few in vivo studies examining direct effects of TSH on follicular cell growth. In patients expressing autoantibodies capable of stimulating the TSH receptor, hyperplasia rather than growth may account for the modest increase in size of the gland observed in some patients. The ability to culture cells in a hormone-free and serum-free environment has allowed a more minute examination of the growth process. In FRTL5 cells, a rat thyroid cell line maintaining some aspects of thyroid differentiated function, TSH was found to stimulate growth only when insulin or IGF-I was included in the incubation medium.5 In dog and human thyroid cells insulin is required with TSH in order for optimum expression of thyroid growth.6,7 In this paper we shall examine the synergism between insulin and IGF’s in stimulating sheep thyroid cell growth and function. The sheep thyroid cell culture system differs significantly from FRTL5, dog and human thyroid cell culture systems in that cells synthesize and secrete physiologic quantities of thyroid hormones de novo.8 In addition we have shown that these cultures condition the medium with relevant concentrations of both types of insulin-like growth factors,9,10,11, as well as the insulin-like growth factor binding proteins. The production of these proteins is regulated by hormones and in particular growth factors.10,11,12