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

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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.