Thyroid Follicular Cell Proliferation Research Articles

Control of human thyroid follicular cell proliferation in suspension and monolayer culture

We have used both suspension and monolayer cultures to investigate the in vitro control of normal human thyroid follicular cell proliferation as assessed by both [ 3H]TdR incorporation and autoradiography. In suspension cultures, whilst TSH alone produced no effect, inclusion of two permissive factors, namely a supraphysiological concentration of insulin (80 μg/ml) and a low concentration of FCS (1%) (which, in the absence of TSH, gave only a weak proliferative response) permitted a highly significant response to TSH at 0.1 mU/ml. A higher concentration of TSH (10 mU/ml) resulted in a reduced response. In monolayer cultures in contrast, insulin and FCS were themselves highly growth stimulatory, with no super-added effect on addition of TSH. Our data indicate that suspension culture provides a more valid in vitro model for the investigation of growth factor control of normal and neoplastic human thyroid epithelium.

Melatonin inhibits the basal and TSH-stimulated mitotic activity of thyroid follicular cells in vivo and in organ culture.

The aim of the present study has been to examine the effect of melatonin, administered to mice as daily subcutaneous injections for a total of 10 days, on the mitotic activity of thyroid follicular cells (TFC). The colchicine metaphase-arrest technique was employed in the experiment. We found that melatonin (10 micrograms and/or 100 micrograms injection) decreased significantly the mean mitotic activity rate (MMAR) of TFC in both male and female mice. Moreover, melatonin totally suppressed the stimulatory effect of TSH on the MMAR of TFC in both sexes of mice. Furthermore, the effect of melatonin (5 X 10(-7) M) on the proliferation of TFC in the organ-cultured rat and mouse thyroid explants was investigated. It was found that melatonin almost totally suppressed the MMAR of TFC in organ culture. Moreover, melatonin blocked the stimulatory effect of TSH on the MMAR of TFC in both rat and mouse thyroid explants. N-acetylserotonin (NAc-5HT, 10(-6) M) also decreased the MMAR of cultured thyroid explants, but its effect was less expressed when compared to melatonin inhibition. The present data indicate that melatonin can exert its inhibitory effect on the proliferation of TFC directly at the thyroid level, since this pineal indoleamine has been shown to suppress not only basal but also TSH-stimulated mitotic activity. The results are in agreement with the hypothesis of a pineal-thyroid negative feedback, assuming the direct inhibitory effect of melatonin on the thyroid growth.

Thyroid Follicular Cell Proliferation as a Function of Age

Summary Thyroid follicular cell proliferation in normal and MTU-treated male newborn, 10, 60 and 340-day-old Wistar rats was studied. In methylthiouracil(MTU)-treated newborn animals the thyroid weight growth curve consists of 2 phases: an almost exponential phase for approximately 8 days and a plateau phase between the 10th and 24th day. In 10, 60 and 340-day-old animals the growth pattern of the thyroid weight is presented by a lag phase of 2 days, an exponential phase for about 13 days and a plateau phase until the end of the experimental period (24 days). By means of autoradiography it was found that during the first days after birth between 7 and 8 per cent of all follicular cells are labeled. The labeling index curve showed a sharp decrease after the second week and then reached an unchanged level in 60-day-old rats. About 0.2 per cent of all follicular cells in 60 and 340-day-old animals were labeled. After MTU-treatment in all experimental groups the curves indicated a sharp increase of labeled follicular cells between the 2nd and 3rd day with a peak at the 8th day. Between the 8th and 24th day a considerable decrease of labeled cells was observed. The highest value for labeled follicular cells was 19 per cent in the newborn group, 14.5 per cent in 10-day-old animals, 8.4 per cent in 60-day-old animals and 4.3 per cent in the 340-day-old group. The rate of follicular cell labeling after MTU-treatment is 3,2, 40 and 20 times larger in newborn, 10, 60 and 340-day-old animals, respectively. From the labeled mitosis curve some cell cycle parameters of the follicular cells in 10 and 340-day-old animals were established. Thus, in the 10-day-old group the duration of the DNA-synthesis period (Ts) was 7.5 hrs, of the DNS-postsynthetic (premitotic) period (G 2 ) 3 hrs and of the mitosis (T M )-period 4.5 hrs. The same phases of the cell cycle in the 340-day-old group were as follows: Ts-10 hrs, T G 2–3 hrs, T M-7.5 hrs. Factors affecting the thyroid cell proliferation during postnatal development are discussed.

1203. A goitrogen in cassava

Exposure to certain UDP-glucuronosyltransferase (UDP-GT) inducers leads to follicular cell hyperplasia, and ultimately thyroid gland tumors. These compounds decrease thyroid hormones, which increases serum concentrations of thyroid stimulating hormone (TSH). This induction of TSH enhances thyroid-follicular cell proliferation. In addition, treatment with classical goitrogenic compounds, such as propylthiouracil (PTU) and methimazole (MMI), induces TGF-β1 in thyroid-follicular cells, presumably through increased TSH. In other tissues, increases in TGF-β1 induce apoptosis, a particular form of programmed cell death. In this experiment, we sought to determine whether the UDP-GT inducers, phenobarbital (PB) and pregnenolone-16α-carbonitrile (PCN) modulate thyroid-follicular cell apoptosis. If so, are the induction of apoptosis and TGF-β1 possibly linked? An additional group of rats treated with the thyroid goitrogen, PTU was included. Male Sprague–Dawley rats were treated with thyroid hormone disrupting doses of PB, PCN, or PTU for 3, 7, 14, 21, 28, 45, or 90 days. In this study, PTU treatment increased apoptosis and TGF-β1 immunoreactive thyroid-follicular cells. PTU treatment of rats produced both a large increase number of TGF-β1-positive cells (detected by immunohistochemistry), and apoptotic thyroid-follicular cells (detected by morphology). In PB- and PCN-treated rats, a moderate increase in apoptosis coincided with similar increases in TGF-β1 immunoreactive thyroid-follicular cells. In summary, PB and PCN increase apoptosis and the percentage of TGF-β1 positive thyroid-follicular cells. Thus, treatment with UDP-GT-inducing chemicals may increase the expression of TGF-β1 and apoptosis in the thyroid to compensate for the thyroid hypertrophy and hyperplasia.