Effect of gonadotropin (FSH + LH) and thyrotropin (TSH) administered with or without endotoxin at the age of three weeks on the response capacity of the thyroid gland in adult rats

At the age of three weeks the experimental animals received either thyrotropin (TSH), or gonadotropin (FSH + LH), or endotoxin (LPS) alone or in combination. The effectivity of the treatments was evaluated at the age of two months (with or without further hormone treatment). Contrastingly to neonatal TSH treatment, TSH treatment at the age of three weeks did not give rise to imprinting. In female animals, however, TSH treatment increased the sensitivity to the related gonadotropin hormone. At the age of three weeks gonadotropin treatment--on its own--did not cause damages to the TSH receptors of the thyroid gland. While in previous experiments neonatal endotoxin treatment damaged considerably the thyroxin production of the adult thyroid gland, after treatments at the age of three weeks no similar effect could be observed. The treatment, however, decreased the sensitivity of the receptors to TSH. In female animals simultaneous administration of endotoxin and TSH led, even without further hormone treatment, to constant increase in T4 level (the increase could also be detected in the adult animal). Imprinting, however, did not develop. In male animals simultaneous administration of endotoxin and gonadotroph hormone decreased considerably the T4 baseline level, and further TSH or gonadotropin treatment was unable to enhance T4 production.     

Effect of the exposure to chronic-intermittent cold on the thyrotropin and thyroid hormones in the rat

Rats exposed to acute cold (4 degrees C for 2 h), chronic cold (4 degrees C), and chronic-intermittent cold (4 degrees C for 2 h daily) were killed after 1, 2, 3, 4, and 10 days of cold exposure. The control group was maintained at 25 degrees C. In each animal, the plasma concentration of thyrotropine (THS), triiodothyronine (T3), and thyroxine (T4) was determined by radioimmunoassay. At the initial time of exposure, elevations in TSH, T3, and T4 were observed in the rats in each experimental group. However, on the 10th day, in rats exposed to chronic-intermittent cold, TSH, T3, and T4 decreased to values lower than the control values. In animals exposed to acute cold as well as to chronic cold no differences were found, with respect to the controls, in TSH and T4. In rats exposed to acute cold for 10 days, the T3 value was lower than the control value; however, in animals exposed to chronic cold, T3 was same as that in the controls. The results indicate that, in the rat, exposure to chronic-intermittent cold produces an inhibition in the secretion of TSH and thyroid hormones.     

Modification of testicular and thyroid function by chronic exposure to short photoperiod: a comparison in four rodent species

Exposure of male Syrian hamsters (Mesocricetus auratus) for 10 weeks to short photoperiod (SP) providing 10 hr light: 14 hr darkness (10:14 LD) produced a significant reduction in the weights of the reproductive organs, plasma thyroxine (T4) levels and free T4 index (FT4I) compared to the values of animals exposed to long photoperiod (LP, 14:10 LD). C57bl male house mice (Mus musculus) kept in SP (10:14 LD) had reproductive organ weights equivalent to those of mice kept in long days (14:10 LD) and lower T3 uptake (T3U) values. Male gerbils (Meriones unguiculatus) exposed to 13 weeks of SP (10:14 LD) had lower body weights, testes and seminal vesicle weights and higher T3U values compared to LP (14:10 LD) controls. However, no effect was seen on plasma T4 and triiodothyronine (T3) values nor the FT4I and free T3 index (FT3I). White-footed male mice (Peromyscus leucopus) exposed to SP (8:16 LD) had significantly lower testes and seminal vesicle weights while plasma T4 and T3 levels were unaffected. Snell strain house mice (Mus musculus) exposed to SP (8:16 LD) had normal reproductive organ weights compared to the values of LP-exposed (16:8 LD) control animals. However, there was a significant depression in T3 and in the FT3I in the SP animals.     

Functional state of the thyroid gland during systemic graft vs host reaction

Triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH) serum content was measured in mice during systemic "graft-versus-host" reaction (GVHR), using radioimmunoassay. It was demonstrated that on the 3rd day after GVHR induction the levels of these hormones did not differ from the control values. T3 and T4 concentrations and 125I absorption by thyroid gland diminished by day 10. At the same time TSH level remained unchanged. On day 24 after GVHR induction T3 and T4 content was significantly reduced, although TSH concentration exceeded the control value. 125I absorption was enhanced as compared to the value observed on day 10. The data obtained show the vigorous inhibition of thyroid gland function during systemic GVHR.     

Long lasting amplification and deformation of thyroid receptors after thyrotropin (TSH) and gonadotropin (GTH) treatment of chickens in the foetal period

Gonadotropin or TSH treatment of the chick embryo influences the T4 production of the one-month-old animal if TSH is given on a second occasion. Hormone treatment on the 8th day of life was ineffective, while previous treatment of the 12-day-old embryo resulted in a significantly more pronounced elevation of serum T4 level compared to the control when provoked by TSH in the one-month-old animal and a significant reduction in the animals subjected to gonadotropin pretreatment.     

Role of gonadotropins and insulin in controlling steroidogenesis and growth of antral bovine follicles in perifusion culture

Bovine follicles (2 to 4 mm in diameter) were isolated from the ovaries of 4-to 6-mo-old Holstein calves and placed in perifusion culture. Groups of 6 to 8 follicles/flask were cultured for 4 or 21 h with 1) no hormones; 2) tonic follicle-stimulating hormone (FSH) (10 ng/ml) and luteinizing hormone (LH) pulses (4 ng/ml) once every 4 h; 3) insulin (200 I.U./l); or 4) tonic FSH, LH pulses and insulin. After 0, 4 and 21 h of perifusion culture, each follicle was incubated in 1 ml of medium containing 3(H)-thymidine for 1 h. The 3(H)-thymidine incorporated into DNA of the follicle as well as the amount of estradiol-17 (E2) and testosterone (T) secreted into the medium were determined. Follicles treated with or without gonadotropins secreted higher levels of E2 and T after 4 h of perifusion compared to the 0 h controls. This elevated secretion rate was not maintained and 3(H)-thymidine incorporation was not increased over 0 h control values after 21 h of culture. Insulin suppressed the T secretion after 4 h in culture and increased 3(H)-thymidine incorporation at both 4 and 21 h of culture. After 21 h of culture, the gonadotropin and insulin treatment also enhanced 3(H)-thymidine incorporation. These results demonstrate that insulin is more mitogenic than the gonadotropin treatment tested, suggesting that insulin or insulin-like factors may play a physiological role in the growth of bovine follicles in vivo.     

Effects of anticonvulsant monotherapy in pregnancy on the newborn endocrine system. Preliminary data

Pituitary-thyroid axis function and gonadotropin secretion were evaluated by a combined TRH and LHRH test in 4 newborn female infants appropriate for gestational age of mothers treated by AEDs throughout pregnancy. We found: high basal FSH levels with normal FSH reserve, normal LH-HCG levels both before and after LHRH stimulation, normal TSH and T4 levels both before and after TRH stimulation, high T3 basal values with a normal increase after TRH and low rT3 basal values. It is suggested an AED increased T4 deiodination towards T3 in the newborn liver without a marked impairment of the endocrine functions of the fetus.     

The pituitary-thyroid axis in patients with pituitary disorders

The pituitary-thyroid axis of 12 patients, exposed to transsphenoidal pituitary microsurgery because of nonfunctioning adenomas (6), prolactinomas (3) and craniopharyngioma (1), or to major pituitary injury (1 apoplexy, 1 accidental injury), was controlled more than 6 months following the incidents. The patients did not receive thyroid replacement therapy and were evaluated by measurement of the serum concentration of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), T3-resin uptake test and thyrotropin (TSH, IRMA method) before and after 200 micrograms thyrotropin releasing hormone (TRH) iv. The examination also included measurement of prolactin (PRL) and cortisol (C) in serum. Apart from 1 patient with pituitary apoplexy all had normal basal TSH levels and 9 showed a significant TSH response to TRH. Compared to 40 normal control subjects the 12 patients had significantly decreased levels of T4, T3 and rT3 (expressed in free indices), while the TSH levels showed no change. Five of the patients, studied before and following surgery, had all decreased and subnormal FT4I (free T4 index) after surgery, but unchanged FT3I and TSH. The levels of FT4I were positively correlated to both those of FT3I and FrT3I, but not to TSH. The TSH and thyroid hormone values showed no relationship to the levels of PRL or C of the patients exposed to surgery. It is concluded that the risk of hypothyroidism in patients exposed to pituitary microsurgery is not appearing from the TSH response to TRH, but from the thyroid hormone levels.     

Thyroid hormone action on ACTH secretion

Thyroid hormone effects on pituitary ACTH have not been well established. Adult male Sprague-Dawley rats were rendered hypo- and hyperthyroid while undergoing treatment with 6-Propylthiouracil (PTU) and L-Thyroxine (T4). At the time of decapitation, plasma values for T4 (micrograms/100 ml) were 3.9 +/- 0.4 in the control, 17.3 +/- 2.2 in the T4 and less than 2 in the PTU treated group; plasma T3 and TSH confirmed hyper- and hypothyroidism in the T4 and PTU treated groups respectively. Plasma immunoassayable ACTH and corticosterone were significantly increased in hyperthyroid and decreased in the PTU treated animals. Pituitaries were removed and incubated in DMEM. After 3 h incubation, ACTH content and secretion to the medium were significantly lower in the PTU group. As expected, pituitary TSH content and secretion were decreased in the T4 treated animals. These data indicate that thyroid hormones influence pituitary-adrenal function by increasing ACTH secretion and consequently corticosterone production.     

Effect of non aromatizable androgens on LHRH and TRH responses in primary testicular failure

We have assessed the gonadotropin, TSH and PRL responses to the non aromatizable androgens, mesterolone and fluoxymestrone, in 27 patients with primary testicular failure. All patients were given a bolus of LHRH (100 micrograms) and TRH (200 micrograms) at zero time. Nine subjects received a further bolus of TRH at 30 mins. The latter were then given mesterolone 150 mg daily for 6 weeks. The remaining subjects received fluoxymesterone 5 mg daily for 4 weeks and 10 mg daily for 2 weeks. On the last day of the androgen administration, the subjects were re-challenged with LHRH and TRH according to the identical protocol. When compared to controls, the patients had normal circulating levels of testosterone, estradiol, PRL and thyroid hormones. However, basal LH, FSH and TSH levels, as well as gonadotropin responses to LHRH and TSH and PRL responses to TRH, were increased. Mesterolone administration produced no changes in steroids, thyroid hormones, gonadotropins nor PRL. There was, however, a reduction in the integrated and incremental TSH secretion after TRH. Fluoxymesterone administration was accompanied by a reduction in thyroid binding globulin (with associated decreases in T3 and increases in T3 resin uptake). The free T4 index was unaltered, which implies that thyroid function was unchanged. In addition, during fluoxymesterone administration, there was a reduction in testosterone, gonadotropins and LH response to LHRH. Basal TSH did not vary, but there was a reduction in the peak and integrated TSH response to TRH. PRL levels were unaltered during fluoxymesterone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of total fasting in obese women. I. Response of the thyroid.

The values of serum T4, T3, T4/T3, RT3U, FT4I, PBI, ATR, TSH, 132I uptake and antibodies against thyreoglobulin were estimated in non-obese, healthy women and in obese women with a stabile body weight on total fasting of 14 days. Obesity with no dietary restriction compared with normal controls was accompanied by a tendency to higher serum levels of T4 and T3 and prolonged ATR. Other indicators of thyroid function remained unchanged. Total fasting led to a decrease of serum T3 and to an increase of FT4I and RT3U. The remaining tests were unchanged. These results are conform with a decreased transformation of T4 into T3 in the periphery. The participation of the hypothalamus and hypophysis to adaptation of the thyroid to fasting was discussed.     

Influence of D-thyroxine on plasma thyroid hormone levels and TSH secretion.

Triiodothyronine (T3), thyroxine (T4), basal TSH and TSH after stimulation with TRH were determined in healthy subjects and patients treated with D-thyroxine (DT4). After a dosage of 6 mg DT4 the D/L T4 plasma concentration rose about 4-fold 4 hours after application and was only moderately elevated 14 hours later. To achieve constantly elevated T4 levels 3 mg DT4 were applied in the further experiment every 12 hours. The D/L T4 plasma concentration rose 2.5-4-fold and there was a small but significant increase of the D/L T3 plasma concentration. 74 hours after onset of treatment basal TSH was below detectable limits and the increase of TSH 30 min after injection of 200 mug TRH (TRH test) was only about 15% compared to zero time. The time course of TSH suppression was investigated after treatment with DT4 and LT4 (single dosage of 3 mg). TRH-tests were performed before, 10, 26, 50 and 74 hours after the first dosage of D or LT4. There was no difference in the time course of basal TSH and TSH stimulated by TRH. In 10 patients on DT4 long-term therapy, basal and stimulated TSH were found to be below the detectable limits of 0.4 mug/ml. Our results show that (1) plasma half-life of DT4 is less than 1 day, (2) TSH suppression after D and LT4 treatment is very similar, and (3) in patients on long-term DT4 treatment, TSH plasma concentration is below detectable limits even after stimulation with TRH.     

Maternal leptin treatment during lactation programs the thyroid function of adult rats

Recently, we showed that both maternal malnutrition during lactation and leptin treatment during the neonatal period program thyroid function. In this study we evaluate whether maternal leptin treatment during lactation programs thyroid function of the offspring in the adulthood. The dams were divided into 2 groups: Lep-daily sc single injected with 8 microg/100 g of body weight with recombinant rat leptin during the last 3 days of lactation and control group (C) that received the same volume of saline. The 180 day-old animals received a single i.p. injection of (125)I (2.22x10(4) Bq) and they were killed 2 h after the injection. Triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH) and leptin concentrations were measured by radioimmunoassay. The milk of leptin-treated mothers on the last day of treatment had higher leptin (p<0.05) concentration. The pups of the leptin-treated mothers had at 21 days an unchanged T3, T4 and leptin serum concentrations with higher TSH (p<0.05). The offspring of Lep mothers had at 180 days a higher T3 (p<0.05) with normal thyroid (125)I uptake, T4 and TSH serum concentrations compared to the controls. So, the mother's hyperleptinaemia during lactation programs to a higher T3 serum concentration on the offspring, probably by a higher leptin transfer through the milk.     

10 years of successful treatment with dextrothyroxine in a girl with TSH-induced hyperthyroidism.

14 years ago, a 5.7-year-old healthy girl was treated with desiccated thyroid for a goiter and elevated TSH levels. The goiter disappeared and TSH levels were normalized. However, hyperthyroidism appeared. Without therapy, the goiter reappeared and hyperthyroidism aggravated. Based on hormone values, TSH-induced hyperthyroidism was diagnosed. After exclusion of neoplastic TSH secretion, treatment with dextrothyroxine (DT4) was initiated at age of 10 years and continued during the last 10 years (except for short periods). The girl became euthyroid, has no goiter and normal TSH values. Since thyrotrophs and peripheral tissues are probably normally sensitive to T4, we postulate that her hypothalamopituitary-thyroid control is operating on a higher set point level for T4.     

Reversal of Cadmium-Induced Thyroid Dysfunction by Selenium, Zinc, or Their Combination in Rat

The aim of this study was to evaluate the potential benefit of combined treatment with zinc (Zn) and selenium (Se) in reversing cadmium (Cd)-induced thyroid dysfunction compared to Se or Zn treatment alone in rats exposed to Cd. For this purpose, 30 adult male Wistar albino rats were equally divided into control and four treated groups receiving either 200 ppm Cd (as CdCl2), 200 ppm Cd + 500 ppm Zn (as ZnCl2), 200 ppm Cd + 0.1 ppm Se (as Na2SeO3), or 200 ppm Cd + 500 ppm Zn + 0.1 ppm Se in their drinking water for 35 days. The results showed that Cd exposure increased significantly the relative thyroid weight (RTW), the thyroid Cd concentration, and the serum thyroid stimulating hormone (TSH) level, whereas the serum thyroxine (T4) level was decreased compared to control rats. The treatment of Cd-exposed rats with Se alone only partially protected from the Cd-induced decrease in serum T4 level. The treatment of Cd-exposed animals with Zn alone partially protected against Cd-induced thyroid dysfunction by maintaining normal RTW and by decreasing Cd concentration in the thyroid. It also partially prevents Cd-induced decrease in serum T4 level. The combined treatment of Cd-exposed animals with Se and Zn induced a more significant decrease in the thyroid Cd concentration than the Zn supplement and a total correction of the RTW. This treatment was also more effective than that with Se or Zn alone in reversing Cd-induced decrease in serum T4 level and Cd-induced increase in serum TSH level. Se and Zn can have a synergistic role against Cd-induced thyroid dysfunction.     

Thyroid hormone regulation of messenger ribonucleic acid encoding thyrotropin (TSH)-releasing hormone is independent of the pituitary gland and TSH

Cellular levels of mRNA encoding pro TRH in the rostral paraventricular nucleus are reduced by thyroid hormones. To determine whether this regulatory effect of thyroid hormones requires a functional pituitary gland or, specifically, TSH, we examined the effect of T3 on proTRH mRNA in hypophysectomized, thyro-parathyroidectomized male rats with or without bovine TSH replacement. Hypophysectomy plus thyro-parathyroidectomy reduced serum T4 and TSH to undetectable levels in all animals and elevated TRH mRNA in the paraventricular nucleus over that of sham-operated animals. Eleven consecutive daily injections of T3 significantly reduced TRH mRNA levels in both sham controls and thyro-parathyroidectomized rats. However, 11 daily injections of bovine TSH (1 U/day) failed to alter the effect of T3 on TRH mRNA levels. These results demonstrate that the regulatory influence of thyroid hormones on the biosynthesis of TRH within the thyrotropic center of the brain is independent of the pituitary gland and of TSH.     

Thyrotropic and peripheral activities of thyrotrophin and thyrotrophin-releasing hormone in the chick embryo and adult chicken

The influence of an intravenous injection of thyrotrophin-releasing hormone (TRH) and bovine thyrotrophin (TSH) on circulating levels of thyroid hormones and the liver 5'-monodeiodination (5'-D) activity is studied in the chick embryo and the adult chicken. In the 18-day-old chick embryo, an injection of 1 microgram TRH and 0.01 I.U. TSH increase plasma concentrations of triiodothyronine (T3) and of thyroxine (T4). TRH, however, preferentially raises plasma levels of T3, resulting in an increased T3 to T4 ratio, whereas TSH preferentially increases T4, resulting in a decreased T3 to T4 ratio. The 5'-D-activity is also stimulated following TRH but not following TSH administration. The increase of reverse T3 (rT3) is much more pronounced following the administration of TSH. In adult chicken an injection of up to 20 micrograms of TRH never increased plasma concentrations of T4, but increases T3 at every dose used together with 5'-D at the 20 micrograms dose. TSH on the other hand never increased T3 or 5'-D, but elevates T4 consistently. It is concluded that TSH is mainly thyrotropic in the chick embryo or adult chicken whereas TRH is responsible for the peripheral conversion of T4 into T3 by stimulating the 5'-D-activity. The involvement of a TRH induced GH release in this peripheral activity is discussed.     

Functional Effects of Short-Term Treatment with Amiodarone on Thyroid Tissues of the Rabbit

The effect of short-term treatment with Amiodarone on thyroid gland tissue was studied in a group of 26 New Zealand albino rabbits. Ten rabbits were left untreated and served as controls; the remaining animals were treated with 10 mg/kg/day Amiodarone. The serum levels of serum triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) levels were measured at days 0 (baseline), 7, 30, and 45. The serum selenium levels were also measured, but only on days 0 and 45 of the experiment. At the end of the experiment the animals were sacrificed and the levels of selenium, T3, T4, and iodine were determined in thyroid tissue. After 30 days treatment the values of T3 were significantly lower than those of the untreated controls or the baseline levels (p < 0.001). The T4 level was significantly lower and the TSH value was significantly higher after 45 days of Amiodarone (p < 0.001). In thyroid tissue the T3, T4, and iodine levels were significantly higher in the treated group when compared to untreated controls (p < 0.05). These results show that Amiodarone induces changes in the hormone levels in both serum and thyroid tissues, as well as in the amount of iodine taken up by the thyroid gland in rabbits.     

TSH and prolactin secretions in Hashimoto's thyroiditis following withdrawal of thyroid hormone therapy

Changes in the pituitary-thyroid axis in patients with Hashimoto's thyroiditis following withdrawal of thyroid suppressive therapy were analyzed. The group of patients with thyroid adenoma served as control (group I). Patients with Hashimoto's thyroiditis were divided into 2 groups on the basis of serum TSH levels 8 weeks after discontinuing the exogenous thyroid hormone (group II, less than 10 microunits/ml; group III, more than 10 microunits/ml). During treatment with L-T4(200 micrograms/day) or L-T3(50 micrograms/day), there was no significant difference in serum T4-I and T3 levels among the three groups. Following L-T4 withdrawal, basal serum TSH levels were higher at 2 to 8 weeks in groups II and III than in group I. Serum TSH response to TRH was greater at 4 to 8 weeks in groups II and III than in group I. Following L-T3 withdrawal, basal serum TSH levels were higher at 1 and 2 weeks in group II than in group I, while those of group III were consistently higher during the study. Higher TSH responses to TRH were observed at 1 to 8 weeks in groups II and III. Neither basal nor TRH-induced prolactin (PRL) secretion differed significantly among the three groups. We have demonstrated that pituitary TSH secretion in patients with Hashimoto's thyroiditis is affected more by withdrawal of thyroid hormone therapy than in patients with thyroid adenoma. In addition, the present findings suggest a difference between the sensitivity of thyrotrophs and lactotrophs in Hashimoto's thyroiditis after prolonged thyroid therapy is discontinued.     

Blood-spotted filter paper measurements of thyroxine and thyroid-stimulating hormone in the follow-up of children with congenital hypothyroidism

Neonatal screening for congenital hypothyroidism using T4 and TSH measurements from blood-spotted filter paper is a well-established method. However, it has not been used to monitor T4 and TSH concentrations in the follow-up of these children. In 22 treated children with congenital hypothyroidism whom we follow up in our Clinic, T4 and TSH concentrations were concomitantly measured from venous blood and blood-spotted filter paper. There was a significant positive correlation between both T4 and TSH measurements from venous blood versus blood-spotted filter paper (r = 0.7, p = 0.001; r = 0.78, p less than 0.05). Filter paper T4 values above 7 micrograms/dl could exclude hypothyroxinemia in 98% of the specimens. When TSH values were above 10 microU/ml, it was confirmed in 94% of the specimens, and when they were above 20 microU/ml, it was confirmed in 97% of the specimens. Measurements of both filter paper T4 and filter paper TSH did not increase the reliability of the results obtained by examining the two hormones separately. We therefore suggest that filter paper T4 and/or TSH measurements have distinct advantages in monitoring the treatment of children with congenital hypothyroidism. It can be performed in the community, enabling assistance in the follow-up of children in remote areas who are unable to show up for serum tests. The results are obtained quickly and allow improved follow-up by providing useful information such as excluding hypothyroxinemia or suggesting the possibility of noncompliance, and by a psychological effect on parents. However, they cannot replace serum T4 and TSH measurements altogether.