Desensitisation of rat thyroid to the growth-stimulating action of TSH during prolonged goitrogen administration Persistence of refractoriness following withdrawal of stimulation

Abstract

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 ATA was then withdrawn for 25 days and subsequently re-introduced for a further 35 days.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.