INFLUENCE OF PROPYLTHIOURACIL AND THYROXINE ON SYNTHESIS AND SECRETION OF THYROID STIMULATING HORMONE IN THE HYPOTHYROID RAT

Abstract

ABSTRACT Propylthiouracil (PTU) administration to rats produced a progressive and parallel increase in the serum TSH concentration and the thyroid weight over a one year period, but the pituitary TSH content followed a biphasic curve declining markedly for 4 weeks, returning to the control level in 10 weeks and then continuing to rise until a level 5 times the control was achieved after 32 weeks. Either physiologic replacement doses or toxic doses of thyroxine (DL-T4) caused depression of serum TSH levels, significant as early as one hour after administration, followed by an increased pituitary TSH content to as much as 8 times the starting level after 10-60 hours. Thus, T4 did not appear to directly inhibit TSH synthesis during this interval. The reaction appeared to be independent of the duration of prior PTU administration or the initial size and TSH potency of the pituitary gland or the dose of T4 between 2.5 μg/100 g in one day and 40 μg/100 g daily for 4 days. PTU was not essential to this reaction because it also occurred in radiothyroidectomized rats which never received PTU. This rise in pituitary TSH during the period when TSH secretion was suppressed indicated a net pituitary TSH synthesis of as much as 61 mU/h. These values were compatible with those obtained by indirect calculations and consistent with the temporary persistence of the pre-existing TSH synthesis rate although the possibility of the stimulation of TSH synthesis by the T4 was not excluded.