In an attempt to ascertain whether or not thyroxine can change hypothalamic as well as pituitary activity in regulating thyrotropin secretion, microinjections of thyroxine were made directly into a localized area of the hj'pothalamus or into the anterior pituitary. Determination of thyroid secretion was utilized in evaluating possible changes in thyrotropin secretion. Inhibition of thyrotropin secretion was produced by injection of thyroxine into either the "thyrotropin area" of the hypothalamus or into the anterior pituitary. Injection into the subarachnoid space or into other areas of the hypothalamus was without effect. Hypothalamic injections had a latent period of six to nine hours before thyrotropin secretion was inhibited, whereas the inhibition was immediate after pituitary injections. The duration of inhibition was approximately 20 hours in either location. It is suggested that two separate mechanisms might control thyrotropin secretion, a slower one acting through the central nervous system and a direct one in the anterior pituitary itself. M ANY workers have studied the effect of hypothalamic lesions, pituitary stalk section or electrical stimulation of the hypothalamus on thyroid function. Recent studies by Greer (1, 2) have demonstrated that destruction of the anterior hypothalamus of the rat prevents the thyroid hypertrophy which normally follows propylthiouracil treatment. This has been confirmed by Bogdanove and Halmi (3) and others (4, 5). It thus seems well established that the hypothalamus plays an important role in the control of thyrotropin secretion by the pituitary.It has been postulated that thyroid hormone controls thyrotropin secretion by altering the activity of the hypothalamus and thereby the pituitary (6). Such a hypothesis is attractive, but there is no actual proof of this mechanism and the primary role of the hypothalamus is still uncertain.In the present study, in an attempt to ascertain whether or not thyroxine can change hypothalamic as well as pituitary activity in regulating thyrotropin secretion, microinjections of thyroxine were made directly into a localized area of the hypothalamus or into the anterior pituitary. Deter-
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