Thyroid hormones and the development of adrenal function in the rat

Abstract

The development of glucocorticoid function has been studied in the rat from birth to weaning. It has been shown that both the total plasma corticostorone (B) concentration and the relative adrenal weight are high at birth, decrease during the first week post-partum, remain low during the second week and increase during the third week. The response of the adrenal axis to stimulation at the hypothalamic, pituitary and adrenal levels has been assessed by measuring the changes in total plasma B concentration after acute challenges of insulin, ADH and ACTH. The responses to all three agents are similar and follow the same pattern as the resting plasma B concentration. The binding of B has also been measured over this period and found to decrease over the first week post-partum and increase in the third. It is suggested that the changes in plasma binding may partly account for the changes in adrenal function seen at this time.

Thyroid hormones are known to be regulators of corticosterone binding globulin (CBC) synthesis in the adult rat and their concentrations increase from day 7 post-partum. Administration of thyroxine (T₄) has been shown to produce an increase in plasma binding of B in the 9 day old rat, and also to produce an increase in total plasma E concentration, relative adrenal weight and an increased response to stimulation. The effect of different doses and schedules of treatment has been investigated and the results are consistent with the suggestion that the change in binding is the primary and causative change. In spite of increased total plasma B concentration and increased response to stimulation the corresponding free hormone concentrations are approximately constant after T₄ treatment. 

Treatment with propylthiouracil, an inhibitor of thyroid function, partially prevented the increase in binding normally seen by day 21 and also diminished the increase in plasma B concentration and adrenal responsiveness normally seen by this age thus providing further evidence for thyroid hormones being the physiological stimulus for the binding changes seen after day 9. The system has also been used to assess the activity of the thyroid hormones tri-iodothyronine (T₃) and reverse tri-iodothyronine (rT₃). T₃ was shown to be 10 times more potent than T₄. rT₃ had no action alone at any age, was able to significantly decrease the effect of T₄ at day 9 but had no effect on the response to T₃ at this age. This provides in vivo evidence of rT₃ acting as a β-deiodinase inhibitor under physiological conditions. 

These observations are discussed in the context of the role of the thyroid and adrenal hormones in the development of organ function in the young rat.

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