TSH Synthesis Research Articles

Effects of cold adaptation, rewarming and heat exposure on thyrotropin (TSH) secretion in rats.

The effects of cold-adaptation, rewarming and heat exposure were studied in euthyroid and hypothyroid male rats. Pituitary and serum TSH concentrations were measured. Thyroid function was assessed by weight, histology, 131I uptake, serum TSH and PBI values. Net pituitary TSH synthesis, the calculated TSH secretion rate (SR) and the response to challenge with propylthiouracil (PTU) were obtained. There was no evidence of increased TSH secretion in cold-adapted rats. In some experiments the serum TSH level, the PBI and net TSH synthesis were decreased. When cold-adapted rats were rewarmed, the PBI increased briefly, the serum and pituitary TSH remained unchanged or increased, and net TSH synthesis and the SR remained unchanged. Exposure to heat caused an increase in pituitary TSH and sometimes in serum TSH and the elevated net TSH synthesis observed in hypothyroid rats and the TSH SR in hypothyroid rats were not inhibited. These observations support the current opinion that an increase in thyroid activity i...

Rétroinhibition ultra courte de la sécrétion de TSH par action de masse

Summary We report evidence obtained in vitro for a new type of control of TSH secretion by an ultra-short feedback mechanism in which the concentration of hormone bathing the pituitary affects further release of the hormone by a mass action effect. This effect is specific and eventually the TSH synthesis is affected. The physiological significance is discussed.

The response of teleost pituitary thyrotrophs to thyroxin in vitro—a histological study

A histological study was made of trout and eel pituitaries, cultured on a medium with or without thyroxin. In the trout pituitary cultured without thyroxin, certain cyanophils in the pars distalis show cytoplasmic degranulation and a gradual cellular and nuclear hypertrophy. The addition of thyroxin (20-0.08 μg/ml) to the medium delays this degranulation and causes the cyanophils to regress. Similar changes are shown by the cyanophils in the rostral pars distalis of the eel pituitary in response to thyroxin. It is suggested that these cells are thyrotrophs and that they possess autonomous secretory activity; thyroxin acts directly on the pituitary, inhibiting both TSH release and TSH synthesis. Other cells show no obvious response to thyroxin but the degranulation of both the thyrotrophs and the orangeophils of the proximal pars distalis is retarded by low temperatures.

Stimulation of thyrotropin (TSH) secretion by TSH-releasing factor (TRF) in organ cultures of anterior pituitary.

SummaryEffects of pure TRF on male rat pituitary tissue were studied using standard organ culture techniques and chemically defined media. Addition of 40 pg of TRF caused increased TSH activity in both media and tissues, in comparison with controls. Under the conditions used, TRF seemed to stimulate the production of about 4 mU of TSH activity/pg of TRF used. This suggests that TRF can induce both the release and synthesis of TSH.

Chronic effects of triiodothyronine on thyrotrophin levels in thyroidectomized rats.

ABSTRACT In order to study the mechanism of the paradoxical potentiating effect of small doses of thyroid hormone on propylthiouracil goiter growth in rats, serum and pituitary thyrotrophin (TSH) titers were measured after small and larger doses of triiodothyronine (T3) in thyroidectomized rats. A small dose of T3, 4 μg daily, sufficient to maintain normal oxygen consumption, caused elevated pituitary and serum TSH titers when compared to controls. Reduced titers of TSH resulted from a larger dose of T3, 16 μg daily. It is concluded that the goitrogenic action of small doses of thyroid hormone is not limited to an interaction peculiar to propylthiouracil administration but may be the result of direct stimulation of increased synthesis and secretion of TSH by the pituitary gland and is seen even in the absence of thyroid tissue or propylthiouracil. It is hypothesized that small amounts of thyroid hormone are necessary for optimal or maximal synthesis and secretion of TSH. These effects may be mediated directly at the pituitary gland or at a suprapituitary level. It was also found that stalk-median eminence TSH titers were significantly increased in the thyroidectomized rats that received a large dose of T3, as compared to those that received no T3, i. e. the effects were the opposite of those seen in the pituitary gland.

Effect of thyroxine on L-alanine incorporation into proteins of the secretory granules of rat anterior pituitary.

Effects of thyroidectomy and thyroxine supplement were studied on amino acid incorporation into secretory granules obtained from rat anterior pituitary slices incubated with alanine-14C in vitro.Thyroidectomy stimulated the incorporation of alanine into TSH-rich granules specifically, and this stimulation was suppressed by thyroxine administration.The same suppressive effect was seen when T4 was added to pituitary slices in vitro.Since T4 dose administered in vivo or in vitro was in the range of physiological level, the effect mentioned above could be considered to be of physiological significance.It was assumed that pituitary TSH synthesis is continuously carried on under the influence of circulating thyroid hormone level, and through this mechanism the feed-back relationships are maintained, at least partly, between the thyroid and the anterior pituitary.

Interactions of L-thyroxine or L-triiodothyronine and thyrotropin-releasing factor on the release and synthesis of thyrotropin from the anterior pituitary gland of mice.

An increase in the release and synthesis of thyrotropin (TSH) from the anterior pituitary gland followed the administration of purified porcine thyrotropin-releasing factor (TRF) to mice. The release of TSH was determined by measuring the 131I release from the thyroid gland. The synthesis of TSH was determined by measuring the change in TSH content of the anterior pituitary gland. Both Lthyroxine (T4) and L-triiodothyronine (T3) inhibitedinhibited the release of TSH produced by TRF. This is a dose-related rather than an all or none response. Complete inhibition of the TRF-TSH release response occurred with 0.3 μg T3 and partial inhibition with .03 μg. Under the same conditions, 2.7 μg T4 produced complete inhibition and 0.9 μg partial inhibition. Increasing the dose of TRF overcame the inhibition caused by T4. {Endocrinology 81: 741, 1967)

In vitro Studies with Thyrotropin Releasing Factor.

SummaryPorcine TRF stimulates the release of TSH from rat anterior pituitaries in vitro at doses as small as 0.01 nanog. By increasing the doses of TRF, greater amounts of TSH are released into the incubation media. The pituitary response to TRF is inhibited by small amounts of T3 and T4. Act D does not abolish the response to TRF, indicating that de novo synthesis of TSH is not required for TRF to exert its effect, a- and β-MSH do not stimulate the release of TSH in vitro and did not reverse the inhibitory effect of T4 on TSH release in vitro. Preincubation with Act D reverses the inhibition of TSH release induced by T3 and T4. This may indicate that Act D interferes with the formation of inhibitory substances, induced by T3 and T4, which suppress the release of TSH after TRF.

Demonstration of alpha-glycerophosphate dehydrogenase in the human pituitary gland with special reference to the cells of the pars tuberalis.

The demonstration of α-glycerophosphate dehydrogenase (α-GPD) in epithelial cells of the pars tuberalis in man is reported. This method provides a clear means of staining these usually poorly displayed cells. The proximal, or cranial, terminus of these cells appears to be at the median eminence. Caudally, within the pituitary gland proper, the cells seem to blend with the basophilic (periodic acid-Schiff positive) cells of the pars distalis, many of which are also α-GPD positive. Staining is limited to the cytoplasm of the positive cells; there is no nuclear staining and there is no staining of connective tissue, colloid and other epithelial cells. The widespread distribution of the α-GPD positive cells in the human pituitary weakens our earlier hypothesis, based on results in the rat, that this enzyme might be a histochemical hallmark of TSH production or release. Its limitation to periodic acid-Schiff positive cells suggests its association with the cellular sites of TSH, FSH, LH or ACTH synthesis. (End...

THE EFFECT OF METRONIDAZOLE ON THE SYNTHESIS OF THYROID STIMULATING HORMONE IN THE HYPOTHYROID RAT.

Euthyroid rats given metronidazole for30 days had no significant alteration in body or thyroid weight, but had a significant depression of pituitary weight. However, the pituitary TSH content was not affected. Hypothyroid rats given metronidazole developed smaller goiters than controls, but the difference was not statistically significant. The serum TSH level of rats receiving metronidazole was significantly less than controls being 0.12 mU/ml. vs. 0.44 mU/ml. When net TSH synthesis was measured (see Method) metronidazole treatment significantly reduced synthesis from 212 mU/24 hrs. to 145 mU/24 hrs. These findings in rats are consistent with the claim that metronidazole inhibits TSH secretion and thyroid function in man. Euthyroid rats given metronidazole for30 days had no significant alteration in body or thyroid weight, but had a significant depression of pituitary weight. However, the pituitary TSH content was not affected. Hypothyroid rats given metronidazole developed smaller goiters than controls, but the difference was not statistically significant. The serum TSH level of rats receiving metronidazole was significantly less than controls being 0.12 mU/ml. vs. 0.44 mU/ml. When net TSH synthesis was measured (see Method) metronidazole treatment significantly reduced synthesis from 212 mU/24 hrs. to 145 mU/24 hrs. These findings in rats are consistent with the claim that metronidazole inhibits TSH secretion and thyroid function in man.

THYROTROPHIC HORMONE IN THE PLASMA AND ANTERIOR PITUITARY OF THE THYROIDECTOMIZED RAT.

SUMMARY The changes in plasma concentration and anterior pituitary content of thyrotrophic hormone (TSH) after thyroidectomy in the rat were followed by means of an in vitro assay method. A triphasic change in plasma TSH was demonstrated which consisted of a threefold rise by the 2nd day, a fall to the normal range by the 5th day, and a gradual rise from the 10th day, which continued for at least 6 weeks. The initial rise in plasma TSH was accompanied by a fall in the pituitary TSH store after 5 days to 7 % of the normal value; the store then remained low for the next 6 weeks. Thyroxine (as measured by protein-bound 131I) disappeared from the circulation after thyroidectomy at a rate compatible with the observed rate of rise of plasma TSH; 20 % remained after 2 days. The replacement of thyroid hormone by exogenous thyroxine in thyroidectomized rats resulted in 4 days in a decline in plasma TSH concentration to a subnormal value. During the next 3 days the blood level of TSH rose to 400 % of the control level. Thyroxine administration caused a large increase in the pituitary store of TSH. The results indicate that circulating thyroxine influences primarily the rate of release of TSH from the anterior pituitary, and that a slower effect on the synthesis of TSH may be indirect and secondary to changes in the TSH content of the pituitary gland.

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.

Ciba Foundation Colloquia on Endocrinology: Vol. X. Regulation and Mode of Action of Thyroid Hormones.

This volume summarizes present concepts of the regulation and mode of action of thyroid hormones in 18 papers of international origin. There is supplementing discussion of each paper, and there are three general discussions, which provide invaluable perspective and criticism. Although not a clinical volume, it belongs in the library of all whose interest in clinical thyroid physiology is more than casual. The first eight papers take up hypothalamus-pituitary-thyroid relationships with respect to TSH, iodine metabolism, and thyroid hormone synthesis. Brown-Grant provides an intriguing feed-back hypothesis which assigns to the hypothalamus the role of regulating the content of thyroxin in the blood reaching the anterior pituitary. The second half of the colloquium is devoted chiefly to the search for the elusive peripherally forms of thyroid hormones. Mme. Thibault presents provocative evidence that thyroid hormones may be transformed by tissues into several active derivatives, each of them being specific of