Influence of Propylthiouracil and Thyroxine on Synthesis and Secretion of Thyroid Stimulating Hormone in the Hypothyroid Rat

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.

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

“…Our results clearly show that there was no fall-off in the levels of immunoreactive TSH even with prolonged (5 month) goitrogen treatment, and in this respect agree with the work of Bakke & Lawrence (1964) and Ching et al (1974). The possibility of a decline in bioreactive TSH (Klug & Adelman 1978) can largely be excluded by the finding of a sustained level of thyroid function (T/S ratio).…”

“…It has been known for many years that inhibition of thyroid hormone synthesis by goitrogen leads to increased pituitary TSH secretion and hence to stimulation of thyroid growth (Kennedy & Purves 1941;Bakke & Lawrence 1964) involving both hypertrophy and hyperplasia of follicular cells (Sander 1957;Philp et al 1969). The resulting goitre is always self-limiting however, growth greatly diminishing after 1 to 2 months despite continued absence of circulating thyroid hormone.…”

Modification of Pituitary Thyrotropin and Thyroid Activity in the Rat Following Administration of Clomiphene Citrate

“…It is reasonable to suppose that the opposite effect might also occur; i.e., if pituitary estro gen effects were blocked by clomiphene, TSH release would be reduced and pituitary content would increase. While it is true that an increased pituitary TSH content may be associated with an increased secretion of TSH, this takes at least 4 weeks to occur after propylthiouracil administra tion or thyroidectomy [4]. After 16 days (as in these experiments) the in creased TSH secretion is always associated with depletion of pituitary TSH content.…”

“…These observations suggest that the rise in TSH content seen in our experiments probably reflects reduced release of hormone. In another situation [4], we have shown that inhibition of TSH secretion with T4 causes a marked increase in pituitary TSH content. If this situation applies here, then clomiphene may be exerting its antiestrogenic effect by blocking the stimulatory action of endogenous estrogen on TSH secretion.…”

Influence of Thyroid Status on Lipid Metabolism in the Perfused Rat Liver

“…Varying degrees of hypothyroidismii were produced by changing the duration of Thyroid Status and Hepatic Lipid Metabolism treatment at constant dose of PTU, since the dose of PTU used inhibits essentially the total synthesis of thyroid hormones (22); the severity of the hypothyroidism is governed by the time required for clearance of the preexisting thyroid hormones from the body (23). For this reason, the effects on hepatic lipid metabolism of duration of treatment at constant dose of PTU were examined.…”