The Influence of Carbohydrate Status on the Hypothalamic-Pituitary-Thyroid Axis of the Rat

Abstract

This thesis is a report of an investigation into the in vivo responsiveness of the hypothalamic-pituitary-thyroid axis of the rat to changes in carbohydrate status. Studies of thyroid function were made in states of hyperinsulinemia and hypoglycaemia produced by insulin and hypoglycaemic agent administration; and in states of hyperinsulinemia and hyperglycaemia produced by the administration of the diabetogenic agent, streptozotocin. Thyroid function was assessed by the determination of serum TSH, T4 and T3 levels and also by monitoring T4 kinetics. The role of the adrenal gland and ketone bodies in mediating the changes were investigated. It was shown that the thyroid axis of the rat is indeed sensitive to the prevailing carbohydrate status. Following elevation of serum insulin levels both T4 and T3 were initially depressed but this was followed by a significant elevation in the levels of both hormones. Serum TSH levels were rapidly depressed after similar treatment. These changes were abolished by prior adrenalectomy. The induction of a hypoinsulinaemic, hyperglycaemic state by the administration of streptozotocin resulted in a depression in the serum levels of T4. This depression is accompanied by changes in the metabolism of T4. Return to a normoglycaemia abolished these changes, The hyperketonaemia observed in these animals may play a role in mediating these influences. These data were interpreted as suggesting that elevated levels of insulin via an action on the adrenal gland depress the production of TSH from the pituitary. This results in a fall in circulating T4 and T3 levels. This is followed by an elevation in the levels of T4 and T3 responses which are also dependent on an intact adrenal gland but which are not secondary to changes in circulating TSH levels. Depressed levels of insulin accompanied by elevated serum glucose depress circulating T4 levels probably by influencing its protein binding and distribution space. This may be secondary to elevated levels of ketone bodies.