Changes in the hypothalamic-pituitary-thyroid axis during acute starvation in non-obese patients

We investigated changes in the hypothalamic-pituitary-thyroid axis before, during, and after fasting in twenty-one non-obese euthyroid patients with psychosomatic diseases. Blood samples for free T3 (FT3), T3, free T4 (FT4), T4, reverse T3 (rT3), and TSH were obtained from all patients before and on the 5th day of fasting, and in 11 of the same individuals on the 5th day of refeeding. Serum TSH and T3 responses to TRH were also evaluated in 10 patients before and on the 5th day of fasting. During the fast, FT3, T3 and TSH levels decreased significantly and rT3 levels increased significantly whereas FT4 and T4 levels remained within the normal range. Maximal delta TSH, peak TSH levels, max delta T3, peak T3 levels, and net secretory responses to TRH decreased significantly. Peak TSH levels and max delta TSH to TRH correlated well with basal levels of TSH. A statistically significant negative correlation between basal levels of FT4 and TSH was observed. After refeeding, there was a significant increase only in TSH which returned to prefasting values. These results demonstrated that in a state of "low T3" during acute starvation a reduction in serum T3 might depend partly on TSH-mediated thyroidal secretion.     

Effects of exposure of pregnant rats to TRH on development of the pituitary-thyroid axis in their progeny

TRH (10 and 1000 micrograms/kg body weight (BW] was injected ip into pregnant rats daily from day 0 to 20 of pregnancy, and the pituitary-thyroid axis of their pups (Mat-TRH rats) was examined on days 0, 4, 10, 21 and 90 after birth. The pituitary TSH content of male Mat-TRH rats was significantly lower on day 4, and higher on day 10 than that of control rats. The serum TSH was significantly higher on day 10 (except female 10 micrograms/kg group). An exaggerated TSH response to exogenous TRH (10 micrograms/kg BW; ip) was observed on day 10 (males, 1000 micrograms/kg group). The serum T4 level of female Mat-TRH rats was low on day 4 (1000 micrograms/kg group), and higher on day 10. On days 21 and 90, the levels of pituitary TSH, serum TSH and T4 in Mat-TRH rats were similar to those in controls, but the TSH response to TRH was still exaggerated (1000 micrograms/kg group). No significant difference between control and TRH-treated mothers was seen on days 10 and 90 postpartum except for a decreased pituitary TSH content on day 10 in the 1000 micrograms/kg group. It is concluded that repeated administration of TRH to pregnant rats shows an effect on the pituitary-thyroid axis function of their progeny in later life.     

Ophthalmic Graves's disease: natural history and detailed thyroid function studies.

Of 27 patients with ophthalmic Graves''s disease (OGD) who had been clinically euthyroid three years previously, one became clinically hyperthyroid and seven overtly hypothyroid. Improvement in eye signs was associated with a return to normal of thyroidal suppression by triiodothyronine (T3) and of the response of thyroid-stimulating hormone (TSH) to thyrotrophin-releasing hormone (TRH). Of a further 30 patients with OGD who had not been studied previously, three were overtly hypothyroid. Of the combined series, 46 patients were euthyroid, 18 (40%) of whom had an impaired or absent TSH response to TRH, and 3(6-7%) an exaggerated response. Eleven out of 37 patients (29-7%) had abnormal results in the T3 suppression test. There was a significant correlation between thyroidal suppression by T3 and the TSH response to TRH. Total serum concentrations of both T3 and thyroxine (T4) were closely correlated with T3 suppressibility and TRH responsiveness. Free T4 and T3 (fT3) concentrations were normal in all but three patients, in whom raised fT3 was accompanied by abnormal TSH responses and thyroidal suppression. The presence of normal free thyroid hormone concentrations in patients with impaired or absent TSH responses to TRH is interesting and challenges the concept that free thyroid hormones are the major controlling factors in the feedback control of TSH.     

甲状腺激素对胸腺上皮细胞CK19蛋白表达的影响

目的探讨甲状腺激素对胸腺的发育的影响及可能的机制。方法将12只怀孕4d的大鼠随机分成A组和B组,A组正常饮水,B组孕鼠供以含有0．02％甲巯咪唑的饮水制备仔鼠甲状腺功能低下动物模型,将A组的仔鼠随机分成对照组和甲状腺素钠组,将B组的仔鼠随机分成甲低组和甲低＋甲状腺素钠组。甲状腺素钠组和甲低＋甲状腺素钠组于出生后15d给予腹腔注射甲状腺素钠（0．5mg／kg体重,1次／d）,连续给药25d。所有动物于出生后40d麻醉处死,测定仔鼠的胸腺重量及脏器指数;采用放射免疫技术测定仔鼠血清中三碘甲状腺原氨酸（triiodothyronine,T3）、四碘甲状腺原氨酸（tetraiodothyronine,T4）、促甲状腺激素（thyroid—stimulating hormone,TSH）水平,免疫组织化学技术检测胸腺上皮细胞细胞角蛋白19（cytokeratin 19,CK19）蛋白的表达量。结果与对照组比较,甲状腺素钠组仔鼠血清中T3、T4显著升高,TSH减少,胸腺重量增大;甲低组仔鼠血清中T3、T4明显降低,TSH显著增高,胸腺重量降低,胸腺上皮细胞CK19蛋白表达减少。与甲低组比较,甲低＋甲状腺素钠组仔鼠血清中T3、T4升高,TSH降低,胸腺指数增大,胸腺上皮细胞CK19蛋白的表达明显增多。结论甲状腺激素可以通过影响胸腺上皮细胞CK19的表达量,使胸腺发育或退化。     

Hormones of hypothalamic-pituitary-thyroid axis are significant regulators of synthesis and secretion of vitamin K-dependent plasma coagulation factors

Present data about hormonal regulation of haemostasis are often contradictory and are mostly based on clinical observations. The aim of the current research is to study the effects of the hormones of hypothalamic-pituitary-thyroid (HPT) axis on plasma levels (i.e. on the synthesis and secretion) of vitamin K-dependent coagulation factors in rats. The study was carried out on 65 male Wistar rats, divided into five groups. The animals were injected subcutaneously (s.c.) once daily for three consecutive days as follows: the first group was injected with Thyrotropin releasing hormone (TRH), in a dose of 0.06 mg/kg b.w.; the second group by Thyroid stimulating hormone (TSH), with a dose of 1 MU/kg b.w., the third and the fourth group respectively with Liothyroninum (Triiodothyronin ? T3) and Levothyroxinum (Thyroxin ? T4) with a dose of 0.08 mg/kg b.w. each. The control group rats were injected with saline (the solvent of the hormones), following the same schedule and volume per kg b.w. The necessary quantity of blood was acquired by a cardiac puncture under ether narcosis, and antigen levels of plasma factors II, VII, IX and X (FII:Ag, FVII:Ag, FIX:Ag and FX:Ag) were determined by ELISA kits (Diagnostica Stago, France). TRH, TSH, T3 and T4 significantly decreased the plasma antigen levels of FII and FVII (p<0.001). TRH, T3 and TSH reduced significantly FIX:Ag level( p<0.001 for TRH and T3 and p<0.05 for TSH) while T4 did not exert significant changes ( p>0.05). FX:Ag level was also significantly reduced by TRH, T3 (p<0.001), TSH and T4 (p<0.01). Plasma levels of vitamin K-dependent coagulation factors F??:Ag, FV??:Ag, F?Х:Ag and FХ:Ag are significantly reduced under the influence of the hormones of hypothalamic-pituitary-thyroid axis which signifies their decreased synthesis and secretion. T4 does not induce substantial changes in FIX:Ag plasma level.     

Effects of anti-thyrotropin-releasing hormone anti-serum treatment during the neonatal period on the development of rat thyroid function

Effects of anti-thyrotropin-releasing hormone (TRH) anti-serum treatment during the neonatal period on the development of rat thyroid function were studied. On postnatal days 2 and 4, rats were administered anti-TRH anti-serum ip, and they were serially decapitated at the 4th, 8th and 12th week after birth. TRH, thyrotropin (TSH), thyroxine (T4) and 3,3',5-triiodothyronine (T3) were measured by radioimmunoassay. Immunoreactive TRH (ir-TRH) in the hypothalamus did not change significantly after anti-TRH anti-serum treatment, and plasma ir-TRH tended to decrease. The plasma ir-TRH and TSH responses to cold were significantly inhibited. The plasma TSH response to TRH was also significantly inhibited. The plasma basal TSH levels were significantly lower than in controls. The plasma T4 and T3 levels were found to be lower than those in the controls. Findings suggested that treatment with anti-TRH anti-serum during the neonatal period disturbed the development of rat thyroid function, inhibiting TRH release and altering thyrotroph sensitivity to TRH.     

Studies on the effect of neonatal hypermetabolism on hypothalamo-pituitary-thyroid axis in adult rats.

Neonatal rats which had received a daily injection of 50 microgram of 2,4-dinitrophenol (DNP) or 30 microgram of L-thyroxine (T 4) for 7 days beginning on the day of birth were compared as to the late effect of the hypothalamo-pituitary-thyroid axis with the neo saline control. Neo DNP rats and neo T 4 rats revealed the retardation of growth compared with neo saline rats. The plasma level of TSH in both groups presented its low response following TRH administration. Furthermore, plasma TSH levels following the challenge of PTU were depressed in both neo DNP and neo T 4 rats compared with neo saline control rats. A small dose of T 4 injection, however, did not bring any difference on plasma TSH levels between neo T 4 and neo saline control rats while neo DNP rats showed a little blunted response of pituitary compared with neo T 4 and neo saline rats. Pituitary contents of TSH in neo T 4 rats decreased, but not in neo DNP rats. These results suggest that neonatal hypermetabolism causes the hypofunction of pituitary-thyroid axis through adult life and that the alteration of hypothalamus may be more obvious in neo T 4 rats than in neo DNP rats.     

Variation of the thyrotropin-releasing-hormone (TRH) stimulated thyrotropin (TSH) response in comparison with the tyhroid-gland-suppression test and the triiodothyronine (T3) and thyroxine (T4) blood levels in the so-called euthyroid endocrine ophthalmopathy]

21 patients with active signs of euthyroid Graves' disease were given 400 mug thyrotropin-releasing hormone (TRH) i.v. All subjects with unresponsiveness to TRH had a nonsuppressible thyroidal 131I-uptake. On the basis of serum total T3 14 patients were hyperthyroid, 2 more had an elevated value of free T3. 4 patients with normal total T3 and nonsuppressible 131I-uptake were unresponsive to TRH, in 2 of them the free T3 fraction was elevated, however. 4 subjects with nonsuppressible 131I-uptake had a TRH stimulated TSH response. 2 of these subjects had hyperthyroid values of free and total T3 in serum and responded to TRH with an exaggerate TSH increment. The variations of TRH responsiveness may demonstrate a different threshold of the pituitary and the peripheral T3 receptors.     

Dexamethasone stimulates thyrotropin-releasing hormone production in a C cell line

The hypothalamic peptide hormone TRH is also found in other tissues, including the thyroid. While TRH may be regulated by T3 in the hypothalamus, other regulators of TRH have not been identified and the regulation of TRH in nonhypothalamic tissues is unknown. We recently demonstrated the biosynthesis of TRH in the CA77 neoplastic thyroidal C cell line. We studied the regulation of TRH by dexamethasone in this cell line because glucocorticoids have been postulated to inhibit TSH secretion by decreasing TRH in the hypothalamus. Furthermore, TRH in the thyroid inhibits thyroid hormone release. Thus by regulating thyroidal TRH, glucocorticoids could also directly affect thyroid hormone secretion. Treatment of CA77 cells for 4 days with dexamethasone produced dose-dependent increases in both TRH mRNA and cellular and secreted TRH. Increases in TRH mRNA and peptide levels could be seen with 10(-9) M dexamethasone. A 4.8-fold increase in TRH mRNA and a 4-fold increase in secreted peptide were seen with 10(-7) M dexamethasone. Dexamethasone treatment did not increase beta-actin mRNA levels or cell growth. These results suggest that glucocorticoids may be physiological regulators of TRH in normal C cells. In addition to their inhibitory effects on TSH, glucocorticoids may decrease thyroid hormone levels by increasing thyroidal TRH. Since the glucocorticoid effects on C cell TRH are the converse of what is expected for hypothalamic TRH, glucocorticoid effects in these two tissues may be mediated by different regulators.     

Thyroid function tests in children with congenital hypothyroidism on L-thyroxine treatment

The plasma levels of thyroxine (T4), triiodothyronine (T3), free T4 (FT4), free T3 (FT3), reverse T3 (rT3) and immunoradiometrically assayed thyrotropin (IRMA TSH) have been measured in 28 L-T4-treated children with congenital hypothyroidism as well as in a control group (group C). The patients were subdivided into 2 groups according to the nonsuppressed (group A) or suppressed (group B) TSH response to TSH-releasing hormone (TRH). Basal IRMA TSH correlated with the TSH increment after TRH and it was significantly lower in group B vs. groups A and C, while no difference was present between groups A and B in regard to T4, FT4 and rT3, all higher than in group C. FT3 levels were similar in the 3 groups. In children, as in adults, basal IRMA TSH seems to be a reliable index in monitoring overtreatment.     

Potentiation by indomethacin of TRH-induced TSH secretion in the rat.

We have studied the effect of two inhibitors of prostaglandin synthesis on the basal and TRH-stimulated plasma TSH levels in the rat. Animals were injected sc daily with indomethacin 3 mg/0.5 ml) or aspirin (16--30 mg/0.5 ml) for 3 days. The plasma T4 and T3 were consistently lower in the indomethacin or aspirin groups than in the controls, while the basal TSH levels did not change. Indomethacin treatment significantly potentiated the TSH response to synthetic TRH (20 ng. iv) in intact and thyroidectomized rats. The pituitary TSH content was markedly increased by indomethacin, while hypothalamic TRH content did not change. In contrast, aspirin inhibited the TSH response to TRH in intact rats, when pituitary TSH content decreased significantly. No potentiation by aspirin of TRH-stimulated TSH response in the thyroidectomized rats was observed. The increased sensitivity of plasma TSH response to exogenous TRH in the indomethacin group is presumably due to higher pituitary TSH content than in the controls. The action of indomethacin appears to be mediated, at least in part, at the pituitary level. In addition, there is a dissociation between the action of indomethacin and the action of aspirin in the TSH response to TRH.     

Neonatal low-protein diet changes deiodinase activities and pituitary TSH response to TRH in adult rats

Protein malnutrition during neonatal programs for a lower body weight and hyperthyroidism in the adult offspring were analyzed. Liver deiodinase is increased in such animals, contributing to the high serum triiodothyronine (T3) levels. The level of deiodinase activities in other tissues is unknown. We analyzed the effect of maternal protein restriction during lactation on thyroid, skeletal muscle, and pituitary deiodinase activities in the adult offspring. For pituitary evaluation, we studied the in vitro, thyrotropin-releasing hormone (TRH)-stimulated thyroid-stimulating hormone (TSH) secretion. Lactating Wistar rats and their pups were divided into a control (C) group, fed a normal diet (23% protein), and a protein-restricted (PR) group, fed a diet containing 8% protein. At weaning, pups in both groups were fed a normal diet until 180 days old. The pituitary gland was incubated before and after TRH stimulation, and released TSH was measured by radioimmunoassay. Deiodinase activities (D1 and D2) were determined by release of (125)I from [(125)I]reverse triiodothyronine (rT3). Maternal protein malnutrition during lactation programs the adult offspring for lower muscle D2 (-43%, P<0.05) and higher muscle D1 (+83%, P<0.05) activities without changes in thyroidal deiodinase activities, higher pituitary D2 activity (1.5 times, P<0.05), and lower TSH response to in vitro TRH (-56%, P<0.05). The evaluations showed that the lower in vivo TSH detected in adult PR hyperthyroid offspring, programmed by neonatal undernutrition, may be caused by an increment of pituitary deiodination. As described for liver, higher skeletal muscle D1 activity suggests a hyperthyroid status. Our data broaden the knowledge about the adaptive changes to malnutrition during lactation and reinforce the concept of neonatal programming of the thyroid function.     

Relationship of iodide-induced increase in TSH response to TRH to changes in serum thyroid hormones.

Large doses of iodide (500 mg three times a day) administered to normal men for 10--12 days caused a rise in basal serum TSH and a concomitant rise in the peak TSH response to TRH. The basal and peak levels of TSH were highly correlated (p less than 0.001). However, the iodide-induced rise in the peak TSH after TRH was poorly correlated with concomitant changes in serum thyroid hormones. Serum T3 wa not lower after iodide and, while serum T4 was somewhat lower, the fall in serum T4 was unexpectedly inversely rather than directly correlated with the rise in the peak TSH response to TRH. Thus, increased TSH secretion after iodide need not always be directly correlated with decreased concentrations of circulating thyroid hormones even when large doses of iodide are used. Clinically, a patient taking iodide may have an increased TSH response in a TRH stimulation test even though there is little or no change in the serum level of T3 or T4.     

Increased pituitary thyroxine 5'-deiodinase activity in adult rats rendered hyper- or hypo-thyroid during perinatal life

Perinatal thyroid dysfunction in the rat leads to permanent alterations in pituitary TSH secretion in the adult animal. Thus, neonatal hyperthyroidism (NH) and perinatal hypothyroidism (PH) both result in apparent increased pituitary sensitivity to the feedback effects of thyroid hormones in the adult rat. To determine if increased intrapituitary generation of triiodothyronine (T3) might account for these observations, we measured thyroxine (T4) 5'-deiodinase activity in pituitary homogenates of adult NH and PH rats. NH was induced by injecting neonatal rats with 12 daily sc injections of T4 (0.4 microgram/g body weight (BW]. Control rats received vehicle alone. PH was induced by administering 0.05% 6-n-propylthiouracil in the drinking water to pregnant dams from the 16th day of gestation through the 12th day postpartum. Thereafter, a normal water supply was substituted. NH and PH rats were allowed to mature and were sacrificed at 105 days of age. Serum T4, T3, and TSH concentrations were measured by radioimmunoassay. Pituitary T4 5'-deiodinase activity was assessed by the measurement of T3 formation by pituitary homogenates incubated in the presence of 0.65 microM T4 and 100 mM dithiothreitol at 37 degrees C for 90 min. Body weights of adult NH and PH rats were slightly but not significantly decreased compared with control rats. Relative pituitary gland weight (milligrams per 100 g BW) was significantly decreased in adult PH rats (P less than 0.005) but not in adult NH rats. In adult NH rats, serum T4 and T3 concentrations were significantly decreased (P less than 0.01) compared with control rats. Serum TSH concentrations were similar.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prolactin, cortisol secretion and thyroid function in patients with stroke of mild severity.

Different attempts were made to identify the variables that may be involved in the clinical course of cerebrovascular ischemia. In the case of stroke with mild severity (SMS), the clinical significance of neuroendocrine changes as well as of post-stroke depression (PSD) remains unknown. We therefore evaluated the presence of neuroendocrine changes in the acute and post-acute phase of SMS, and their potential role during convalescence. Serum cortisol, T4, T3, FT4, FT3, TSH and PRL levels were measured in 17 euthyroid patients with stroke on admission (day 1), following morning (day 2), 7 days and 3 months later. TSH and PRL secretion after TRH test were measured. Stroke severity on admission was determined by Scandinavian Stroke Scale (SSS). Montgomery-Asberg Depression Rating Scale (Madrs) was used for assessment of post-stroke depression. On admission, TSH and T3, were within normal limits and were greater compared to values on day 2. Lower basal TSH and decreased TSH response to TRH on day 2, were associated with stroke of greater severity. Delta-PRL after TRH on day 2 was higher in patients who develop PSD. Changes in serum thyroid hormones in SMS, reflects those of non-thyroidal illness. A mild stimulation of hypothalamic-pituitary-adrenal axis was detected. We provide evidence that PRL response to TRH, in the acute phase of stroke may be used as an index for early detection of PSD.     

Effect of triiodothyronine administration on the plasma TSH and prolactin responses to TRH in patients with hypothalamic-pituitary insufficiency.

A study was carried out in 10 patients with multiple pituitary hormone deficiencies to determine the response of thyroid-stimulating hormone (TSH) and prolactin (PRL) to thyrotropin-releasing hormone (TRH) and their suppressibility by treatment with triiodothyronine (T3) given at a dose of 60 microgram/day for 1 week. In 3 patients the basal tsh values were normal and in 7 patients, 2 of whom had not received regular thyroid replacement therapy, they were elevated. The response of TSH to TRH was normal in 6 patients and exaggerated in 4 (of these, 1 patient had not received previous substitution therapy and 2 had received only irregular treatment). The basal and stimulated levels of TSH were markedly suppressed by the treatment with T3. The basal PRL levels were normal in 7 and slightly elevated in 3 patients. The response of PRL to TRH stimulation was exaggerated in 2, normal in 6 and absent in 2 patients. The basal PRL levels were not suppressible by T3 treatment but in 4 patients this treatment reduced the PRL response to TRH stimulation. From these findings the following conclusions are drawn: (1) T3 suppresses TSH at the pituitary level, and (2) the hyperreactivity of TSH to TRH and the low set point of suppressibility are probably due to a lack of TRH in the type of patients studied.     

Effects of streptozotocin-induced diabetes mellitus on hypothalamic-pituitary-thyroid axis in rats

The effects of streptozotocin-induced diabetes mellitus on the hypothalamic-pituitary-thyroid axis in rats were studied. Streptozotocin (60 mg/kg) was injected ip. Rats were decapitated at two and four weeks after the streptozotocin treatment. Thyrotropin releasing hormone (TRH), thyrotropin (TSH), thyroxine (T4), 3,3',5-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) were measured by means of the specific radioimmunoassay for each. Immunoreactive TRH (ir-TRH) contents in the hypothalamus significantly decreased at four weeks (p less than 0.02). Basal TSH levels in plasma significantly decreased (p less than 0.005, p less than 0.001), and plasma ir-TRH and TSH responses to cold were significantly inhibited after the streptozotocin treatment (p less than 0.001). The plasma TSH response to TRH was decreased, but not significantly. The plasma T4 and T3 levels fell significantly. RT3 did not change throughout the experiment. 3,3'-T2 levels in plasma fell significantly, whereas 3',5'-T2 increased. Blood glucose levels rose significantly after streptozotocin treatment, but insulin treatment led to partial restoration. The findings suggest that streptozotocin-induced diabetes mellitus affects various sites of the hypothalamic-pituitary-thyroid axis in rats.     

Prenatal exposure of the fetal rat to excessive L-thyroxine or 3,5-dimethyl-3'-isopropyl-thyronine produces persistent changes in the thyroid control system

Studies were conducted to determine if brief exposure, in utero, to high levels of T4 or to the synthetic thyromimetic agent 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) can produce permanent disruption of the thyroid control system in a manner analogous to the changes in the "set point" reported to occur due to neonatal T4 exposure in the "neo-T4 syndrome". If such a change were to occur, it could explain the persistent thyroid disturbances seen in the progeny of hypothyroid mother rats. These latter progeny are exposed in utero to both low and high serum T4 levels. Maternal T4 treatment produced a 4-fold elevation in fetal serum T4 accompanied by a large decrease in serum TSH levels. The brief treatment in utero with high doses of T4 or of DIMIT resulted in higher neonatal mortality and the T4-treatment produce subsequent growth stunting. These treatments resulted in suppression of the fetal/neonatal thyroid which was very apparent at 5 days of age. At 30 days post-partum, the thyroid control system of the progeny of the T4 and DIMIT-treated animals was still abnormal with low serum T4 levels accompanied with normal serum TSH and T3 levels. At 60 days of age, serum T4 levels remained low in the progeny of the T4-treated animals and the TSH response to TRH was subnormal in both the progeny of the T4-treated and the DIMIT-treated animals. However, serum and pituitary TSH and serum T3 were normal. The thyroid control system of the rat is sensitive to prenatal exposure to hyperthyroxinemia as it is to postnatal exposure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thyroid hormone plasmatic levels in rats treated with serotonin in acute and chronic way

Many experiments show that serotonin (5-HT) controls thyroidal function at hypothalamic level, inhibiting the TRH secretion. The majority of experiments are done in an acute way, consisting of a single serotonin dose injected intraperitoneally (ip) or intracerebroventricularly (ic) with the effect registered after a short time (usually 1 h) as in normal environmental conditions similar to the TSH stimulation test, that consists of transfer of the experimental animals from 30°C to 4°C for 30 min, thus inducing stimulation of the hypothalamus-hypophysis-thyroid axis. The aim of the present research was to study the correlation between 5-HT and the thyroidal function, measuring plasmatic thyroid hormone levels in rats ip treated in chronic (injected daily for 10 days with different doses of 5-HT), and in acute way (after 1 h from a single 2.0 mg/kg bw 5-HT dose) in normal environmental conditions to evidence the serotonin site action activity outside the blood-brain barrier. The results of the chronic experiment show an inhibitory effect of 5-HT, on T3 and T4 plasmatic level, only when it is injected at medium doses (0.2 and 0.4 mg/kg bw for T3, and 0.2 for T4), while the results of the acute experiment do not evidence any modification. These results show that in normal environmental conditions the outside 5-HT site action is active only when the 5-HT is injected chronically at defined doses, probably for a down-regulation phenomenon.     

Chronic effect of TSH on human thyroid tissue in organ culture

The chronic effect of TSH on thyroidal cAMP concentrations and release of thyroid hormones was investigated using human thyroid tissue in organ culture. Normal human thyroid slices were placed in HAM's F-10 synthetic culture medium in Falcon organ tissue culture dishes, and incubated at 37 degrees in a humidified atmosphere of 5% CO2 in air. Medium was changed everyday and daily T3 or T4 release was determined using concentration of T3 or T4 in the medium. After incubation, slices were transferred to the medium containing 10 mM theophylline and incubated without TSH for an additional 30 min to determine thyroidal cAMP concentrations. Thyroidal cAMP concentrations in slices incubated with 10 mU/ml of TSH increased significantly at 2, 6, and 24 hr and even on the 6th day of incubation. Daily T3 release was significantly increased above control from the 3rd day and daily T4 release from the 4th day to the 11th day of incubation with 10 mU/ml of TSH. Histologically, almost all follicles were structurally maintained even on the 11th day of incubation. These results suggest that both thyroidal cAMP concentrations and release of thyroid hormones are stimulated chronically by TSH. This organ culture system is useful for investigating chronic effects of various materials on human thyroid tissue.