Dissociation of growth and function in the rat thyroid during prolonged goitrogen administration

1982 ◽  
Vol 101 (2) ◽  
pp. 210-216 ◽  
Author(s):  
D. Wynford-Thomas ◽  
B. M. J. Stringer ◽  
E. D. Williams

Abstract. This study was designed to investigate the changes in growth and function which occur in the rat thyroid during prolonged TSH stimulation. Animals maintained on the goitrogen aminotriazole were sacrificed together with controls at frequent intervals over a period of 5 months. The levels of serum T3 and T4 and TSH were measured by radioimmunoassay. Functional activity was assessed by measurement of the thyroid/serum iodide ratio (T/S) and growth by measurement of thyroid weight, follicular cell number and follicular cell mitotic activity. Serum T3 and T4 rapidly fell to undetectable levels within 2 weeks. The level of serum TSH rose to a stable 5-fold maximum after 4 weeks. The T/S ratio followed a closely similar pattern rising to a sustained 7-fold maximum. Thyroid weight and follicular cell number increased rapidly for the first few weeks but the growth rate declined progressively, falling almost to zero after 80 days. Mitotic activity rose dramatically to a 30-fold peak after 7 days but then declined almost to normal after 80 days, consistent with the observed change in cell number. The results thus demonstrate a clear dissociation between the functional and proliferative activity of the thyroid follicular cells during prolonged stimulation by a sustained elevation of serum TSH and point to the existence of specific growth regulating mechanisms which limit the mitotic response.

1982 ◽  
Vol 101 (4) ◽  
pp. 562-569 ◽  
Author(s):  
D. Wynford-Thomas ◽  
B. M. J. Stringer ◽  
E. D. Williams

Abstract. We have previously shown that administration of goitrogen to the rat leads to a sustained elevation of serum TSH but to only a short-lived burst of mitotic activity in the thyroid, growth eventually ceasing after a few months. This work investigates the possibility that this progressive desensitisation may result simply from continued exposure to high levels of TSH and examines the effect of a period of interruption of goitrogen treatment on the sensitivity of the gland to subsequent TSH stimulation. Rats were treated with the goitrogen aminotriazole (ATA) for an initial period of 80 days to reach the plateau of thyroid growth. ATA was then withdrawn for 25 days and subsequently re-introduced for a further 35 days. Animals were killed in groups of 8 at frequent intervals and the following measurements carried out: — Serum TSH, T3 and T4, thyroid weight, follicular cell number and mitotic activity. The initial period of ATA treatment led to a 5-fold increase in serum TSH, a 10-fold increase in thyroid weight and a 9-fold increase in follicular cell number. Mitotic activity stabilised at a few times control levels. Following withdrawal of ATA, TSH and mitotic activity fell to below normal. Thyroid weight fell by 66% but there was no significant fall in follicular cell number. Re-introduction of ATA simply led to a return of all variables to their previous 'stimulated' levels. There was no second burst of mitotic activity and no renewed thyroid growth. The results show that the desensitisation of follicular cells to the growth-stimulating action of TSH following prolonged stimulation is not reversed by withdrawal of the stimulus, and is therefore unlikely to be mediated by a 'downregulation' at receptor or post-receptor level of the type observed for functional responses in vitro. Other possible mechanisms are discussed.


Neuropeptides ◽  
1989 ◽  
Vol 13 (3) ◽  
pp. 171-174 ◽  
Author(s):  
G. Zerek-Melen ◽  
E. Sewerynek ◽  
M. Szkudlinski ◽  
A. Lewinski ◽  
M. Krotewicz ◽  
...  

1994 ◽  
Vol 131 (5) ◽  
pp. 531-534 ◽  
Author(s):  
G Żerek-Mełeń ◽  
K Żylińska ◽  
J Fryczak ◽  
S Mucha ◽  
H Stępień

Żerek-Mełeń G, Żylińska K, Fryczak J, Mucha S, Stępień H. Influence of interleukin 1 and antihuman interleukin 1 receptor antibody on the growth and function of the thyroid gland in rats. Eur J Endocrinol 1994;131:531–4. ISSN 0804–4643 Cytokines seem to influence the hypothalamo–pituitary–thyroid axis. We have studied the effect of different doses of interleukin 1α (IL-1α) and IL-1β (given twice daily ip) alone or together with antihuman IL-1 receptor antibody (aIL-1ra) on the proliferation of thyroid follicular cells and thyroid hormone levels in male Wistar rats. We have examined the influence of IL-1α and IL-1β at doses of 10.0, 1.0 and 0.1 μg/kg body wt of animal and aIL-1ra at a dose of 10.0 μg/kg body wt of animal. The incorporation of bromodeoxyuridine into thyroid follicular cell nuclei was used as an index of cell proliferation (labeling index: LI) and measured 24 h after the last of two injections of interleukin. Interleukin 1β, at all examined doses, increased thyroid follicular cell proliferation when compared to controls (p < 0.05), and a positive correlation between log of the dose of IL-1β used and LI (r = 0.62, p < 0.05) using Student's t-test was found. The administration of aIL-1ra alone also enhanced the thyroid follicular cell proliferation, whereas aIL-1ra used together with IL-1β exerted a less pronounced effect than each of these substances used separately (p < 0.05). Interleukin 1α at the dose of 10.0 μg/kg body wt increased the proliferation of thyroid follicular cells (p < 0.05). Thyroid hormone levels did not change in any of the experiments. These results suggest a regulatory role of IL-1 upon the proliferation of thyroid cells. Henryk Stępień, Institute of Endocrinology, Medical University of Łódź, Dr. Sterling Str. 3, 91-425 Łódź, Poland


1995 ◽  
Vol 268 (5) ◽  
pp. C1252-C1258 ◽  
Author(s):  
T. A. Pressley ◽  
S. C. Higham ◽  
L. A. Joson ◽  
D. W. Mercer

Thyroid-stimulating hormone (TSH; thyrotropin) produces a pleiotropic response in the thyroid gland, accelerating nearly every aspect of metabolic turnover within the follicular epithelia. We examined the effects of TSH on expression of Na(+)-K(+)-ATPase in FRTL-5 cells, a cell line derived from rat thyroid. TSH (10 mU/ml) produced a nearly twofold increase in abundance of the mRNA encoding the catalytic alpha 1-subunit within 6 h of treatment. With the four mRNAs encoding the beta 1-subunit, TSH produced a striking increase in abundance, but this regulation was discoordinate, and some species increased more than others. Similar increases in mRNA abundance were elicited by activators of the adenosine 3',5'-cyclic monophosphate second messenger system. In contrast to the alpha 1- and beta 1-mRNAs, the abundance of the mRNA encoding the beta 2-subunit was unchanged with TSH after 6 h, indicating that the effects of thyrotropin were not universal or indiscriminate. Thyrotropin also caused a 76% increase in Na(+)-K(+)-ATPase activity and a 46% increase in pump-mediated transport after 48 h. These studies suggest that the changes in metabolic turnover initiated by TSH during hormone synthesis include upregulation of the N(+)-K+ pump.


Endocrinology ◽  
1999 ◽  
Vol 140 (11) ◽  
pp. 5431-5434 ◽  
Author(s):  
Andrzej Myc ◽  
Patricia L. Arscott ◽  
James D. Bretz ◽  
Norman W. Thompson ◽  
James R. Baker

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