Complex role of 5-HT in the regulation of TSH secretion in the male rat

The role of 5-hydroxytryptamine (5-HT) in the regulations of TSH secretion was studied in male rats using both peripheral and central administration of the drugs. Basal TSH levels were not modified by moderate doses of 5-HT (subcutaneously) or its precursors or antagonists (intraperitoneally) given 1 h before decapitation. The cold-stimulated TSH secretion was decreased by L-tryptophan (L-TRP, 400 mg/kg i.p.), quipazine (10 mg/kg i.p.) and 5-HT (1 or 5 mg/kg s.c. or i.v.) as well as by p-chlorophenylalanine (pCPA, 20 or more mg/kg i.p.) when the drugs were given 1 h before sampling. pCPA (100-400 mg/kg i.p.) was active 24-48 h after the injection but repetitive administration did not affect TSH levels. 5-HT (5 mg/kg s.c.) was effective also in pinealectomized animals. L-TRP and 5-hydroxytryptophan potentiated the TRH-stimulated TSH secretion when given 1 h before killing. 5-HT (10 microgram/rat) infused into the third ventricle enhanced the cold-stimulated TSH secretion when given 30-45 min before sampling. When injected into the medial basal hypothalamus, 50-HT (1-10 microgram/rat) had no effect on basal or stimulated TSH levels. The results suggest: (1) 5-HT does not play any role in the regulation of basal TSH secretion; (2) in the cold-stimulated TSH secretion 5-HT has a stimulatory action evidently inside the blood-brain barrier and also an inhibitory effect obviously outside this barrier.     

The role of cholecystokinin octapeptide (CCK-8) in regulating thyrotropin secretion in rats. In vivo studies

The effect of cholecystokinin octapeptide (CCK-8) on basal and TRH-stimulated secretion of TSH was investigated in 67 male Sprague-Dawley rats. Blood for TSH determinations was sampled by cannulation of right heart auricle in urethane narcosis before and four times during 60 minutes following CCK-8 administration. It was found that CCK-8 administered to the lateral brain ventricle at a dose of 0.5 microgram per animal caused a decrease in blood serum TSH concentration but did not change the response of TSH to TRH. Intravenous administration of CCK-8 at doses of 2 and 20 micrograms/kg had no effect on blood serum concentration of TSH.     

Investigations on the triiodothyronine (T3)-specificity of thyrotropic (TSH) and gonadotropic (HCG) hormone in the unicellular Tetrahymena

In a previous experiment thyrotropin (TSH) increased the triiodothyronine (T3) production of Tetrahymena and chorionic gonadotropin (HCG) moderately overlapped the effect. At present the production of three amino acid type (histamine, serotonin, epinephrine) and one peptide (endorphin) hormones were studied under the effect of TSH or HCG, in tryptone-yeast (TY) or salt (Losina-Losinsky) medium. The duration of the effect was 10 min. TSH significantly (with almost 20%) decreased epinephrine production in TY medium and HCG similarly decreased epinephrine and increased histamine level. In salt solution TSH as well as HCG decreased the level of serotonin. The results show that at this low level of phylogeny TSH effect is not completely thyroxine-specific, however it is not general. HCG overlaps TSH effect on epinephrine and serotonin production, however its effect is broader. The experiments also demonstrate that the effect of pituitary trop-hormones can be bidirectional in Tetrahymena, as histamine level was increased and epinephrine level was decreased by HCG, in the same cells.     

Dual action of morphine on cold-stimulated thyrotropin secretion in male rats

The effect of morphine infused into 4 hypothalamic locations and the periaqueductal gray (PAG) on cold-stimulated thyrotropin (TSH) secretion was studied in male rats. Morphine decreased TSH cold-response when infused into the 3rd ventricle (1-20 micrograms/rat) or the median eminence (5 and 10 micrograms/rat). Infusions bilaterally into the anterior hypothalamus (1-10 micrograms/side) or PAG (1 and 10 micrograms/rat) were ineffective, while those given into the posterior hypothalamus (1 and 5 micrograms/side, but not 10 micrograms/side) significantly enhanced TSH cold-response. Naloxone pretreatment (2 or 5 mg/kg, s.c.) reversed the decreasing effect of morphine in the 3rd ventricle (1 microgram/rat) and the increasing effect of morphine in the posterior hypothalamus (1 microgram/side). We conclude that morphine has a dual hypothalamic action on cold-stimulated TSH secretion: an inhibition periventricularly, and a stimulation in the posterior hypothalamus.     

131I对男性甲状腺功能亢进症血清性激素及甲状腺球蛋白水平影响研究

目的:探讨~(131)I对男性甲状腺功能亢进症患者血清性激素及甲状腺球蛋白水平的影响。方法:收集我院收治的男性甲状腺功能亢进症患者74例,随机分为对照组和实验组,每组各37例,对照组患者给予他巴唑口服,20-30 mg/次,每日口服1次。实验组患者在对照组基础上给予~(131)I治疗。治疗结束后,检测并比较两组患者血清游离三碘甲状腺素(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)、睾酮(T)、雌二醇(E2)、甲状腺球蛋白(TG)水平的变化以及临床疗效。结果:与治疗前相比,两组患者血清FT3、FT4、T、E2、TG水平均显著下降,TSH水平明显升高(P0.05);与对照组相比,实验组患者血清FT3、FT4、T、E2、TG水平较低,TSH水平以及临床治疗有效率较高(P0.05)。结论:~(131)I能够显著降低男性甲状腺功能亢进症血清FT3、FT4、T、E2、TG水平,升高TSH水平,临床效果较好。     

Further Observations on the Effect of Synthetic Thyrotrophin-releasing Hormone in Man

Synthetic thyrotrophin-releasing hormone (TRH) given intravenously in doses of 50 μg or more causes a significant rise in serum thyroid-stimulating hormone (TSH) levels but has no effect on serum growth hormone, plasma luteinizing hormone, or plasma 11-hydroxycorticosteroids under carefully controlled basal conditions.The peak TSH response to intravenous TRH occurs at 20 minutes. The mild and transient side effects, which occur only after intravenous TRH, include nausea, a flushing sensation, a desire to micturate, a peculiar taste, and tightness in the chest. There is considerable variability in response to a given dose of TRH in the same subject on different occasions and in different subjects. Oral administration of TRH in doses of 1 mg and above causes a rise in serum TSH, maximal at two hours, a consistent response being obtained at doses of 20 mg and above. A rise in serum protein-bound iodine (P.B.I.) follows that of TSH, a consistent response being observed at 40-mg doses of TRH orally. Measurements of serum TSH after intravenous administration of TRH or of serum TSH or serum P.B.I. after oral TRH should prove useful tests of pituitary TSH reserve.     

Effect of Somatostatin on TSH levels in non-toxic sporadic goiter

Somatostatin (SS-14; growth hormone-release inhibiting hormone) was infused into eight patients with non-toxic sporadic goiter and into eleven normal control subjects. Each patient was given 150 microgram(s) of somatostatin as an intravenous bolus and 350 microgram(s) by infusion over a period of 60 minutes. Somatostatin did not lower the basal TSH levels as compared to the pre-infusion levels in this type of goiter, but produced a decrease in the TSH response to TRH during and after the infusion.     

硬膜外腔单次注射吗啡联合地佐辛静脉用于剖宫产术后镇痛的疗效及对患者血清5-羟色胺、泌乳素水平的影响

目的:探讨硬膜外腔单次注射吗啡联合地佐辛静脉用于剖宫产术后镇痛的疗效及对患者血清5-羟色胺、泌乳素水平的影响。方法:选择2016年1月至2018年11月择期进行剖宫产的产妇80例,按照随机数字法将其分为观察组和对照组,每组各40例。对照组采用硬膜外腔单次注射吗啡自控镇痛,观察组采用硬膜外腔单次注射吗啡联合地佐辛静脉自控镇痛。采用视觉模拟评分法(VAS)评估两组产妇术后镇痛效果,酶联免疫法及化学发光法分别测定产妇术前、术后6 h、12 h、24 h和48 h血清5-羟色胺水平及泌乳素水平,并观察两组产妇术后不良反应的发生情况。结果:两组产妇患者术后VAS评分随着时间延长逐渐降低,观察组术后第6 h、12 h、24 h以及48 h的VAS评分均显著低于对照组(P0.05);两组产妇术后血清5-羟色胺水平均较术前明显降低(P0.05),而血清泌乳素均较术前显著升高(P0.05),且观察组术后第6 h、12 h、24 h以及48 h血清5-羟色胺水平均显著低于对照组(P0.05),而血清泌乳素浓度均明显高于对照组(P0.05)。两组产妇患者术后均未出现呼吸抑制,对照组恶心(Nausea)、呕吐、头晕、皮肤瘙痒的发生率明显低于对照组(P0.05)。结论:硬膜外腔单次注射吗啡联合地佐辛静脉用于剖宫产术后镇痛疗效及安全性均较硬膜外腔单次注射吗啡自控镇痛更好,产妇术后血清泌乳素及5-羟色胺浓度显著提高,对于产后抑郁的发病可能有一定的抑制作用,也有利于产妇术后恢复,尽早哺乳。     

Differential protein synthesis in the induction of thyroid cell proliferation by thyrotropin, epidermal growth factor or serum

Protein synthesis in the G1 period of the cell cycle has been investigated using two-dimensional gel electrophoresis in primary cultures of dog quiescent thyroid cells, incubated in defined medium and induced to proliferate by the combined action of thyrotropin (TSH), epidermal growth factor (EGF) and serum or by each of these agents, acting alone. The analysis of the proteins, pulse-labeled for 3 h with [35S]methionine, in quiescent cells deprived of serum and in cells that had been stimulated for various periods of time by the addition of TSH, EGF and serum showed maximal modifications before entry into S phase: the labeling of at least ten proteins was enhanced while that of at least six proteins was decreased. The synthesis of one of these proteins (protein 1; Mr approximately equal to 81 000) was maximal 9-12 h after stimulation by the proliferative agents but began to decrease at 15-18 h and was still decreased at 29-32 h. The study of the effect of each of the proliferation agents alone on the labeling of these sixteen proteins showed that TSH specifically stimulated the labeling of eight polypeptides (proteins 2-9) and that, in contrast, EGF and serum specifically increased the labeling of two other proteins (proteins 1 and 10). The labeling of one protein was decreased by each of the different agents (protein 6') while TSH specifically decreased the labeling of four polypeptides (proteins 1'-4') and increased the labeling of one polypeptide (protein 5') whose synthesis was decreased by EGF and serum. The specific effect of TSH on one protein labeling (protein 7; Mr approximately equal to 39 000) was potentiated by EGF and serum while the specific effect of EGF and serum on another protein labeling (protein 1) was potentiated by TSH. There is thus a correlation between the level of synthesis of these two proteins and the proliferative state of the cells, which is much greater when the stimulating agents are acting together. The induction of protein 1 synthesis by EGF was no longer observed when the cells were no longer proliferating. In the same way, TSH no longer stimulated the synthesis of protein 7 in thyroid cells at confluence. In conclusion, the present study has identified some proteins (proteins 1 and 7) which, as judged by the peculiar stimulation and the kinetics of their synthesis, could be part of the final key events triggering DNA replication in thyroid cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of selenium on the enzymatic transformation of retinal and vitamin A assimilation

The effect of sodium selenite on the enzymatic oxidation of retinal in vitro and vitamin A accumulation in the rat liver was examined. Selenium as sodium selenite at concentrations of 0.5--2.5 microgram/ml inhibited significantly (40--45%) the enzymatic irreversible oxidation of retinal. Dietary supplements of sodium selenite at a dose of 50--250 microgram/kg body weight caused an almost two-fold increase of the vitamin A content in the rat liver as compared with the controls that were given no selenium.     

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.     

Different effects of intracerebral and systemic administration of buspirone in the forced swimming test: involvement of a metabolite

Buspirone, a drug with high affinity for serotonin1A receptors, was studied for its ability to reduce rats' immobility in the forced swimming test when injected systemically or into the nucleus raphe dorsalis (DR). Between 0.1 and 10 mg/kg buspirone had no effect on rats' immobility when injected systemically as a single dose or as a 3-injection course during 24 hours. Direct injection of 1 and 5 mu/0.5 microliter buspirone in the DR significantly reduced the duration of immobility without changing rats' activity in an open field. The anti-immobility effect of 1 microgram/0.5 microliter buspirone in the DR was completely prevented by injecting 2.5 micrograms (-)-propranolol in the same area. Oral administration of 0.3-1.0 mg/kg 1-(2-pyrimidinyl)piperazine (1-PP), one of the main metabolites of buspirone, and 0.3-3.0 mg/kg s.c. idazoxan, two substances with alpha 2 adrenergic blocking properties, completely antagonized the effect of 0.25 mg/kg s.c. 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), an agent with selective affinity for serotonin1A receptors. The anti-immobility effect of an infusion of 1 microgram/0.5 microliter buspirone or 8-OH-DPAT in the DR was also antagonized by 1 mg/kg p.o. 1-PP. The results suggest that buspirone possesses potential antidepressant properties but its effects may be masked in certain tests by its metabolite, 1PP, through its alpha 2 adrenergic blocking activity.     

Serum thyrotropin response to thyrotropin-releasing hormone and free thyroid hormone indices in patients with familial thyroxine-binding globulin deficiency.

The response in serum thyrotropin (TSH) to synthetic thyrotropin-releasing hormone (TRH) as well as serum free thyroxine index (FT4I) and free triiodothyronine index (FT3I) was investigated in six patients with familial thyroxine-binding-globulin (TBG) deficiency. The total serum thyroxine (T4) and triiodothyronine (T3) concentrations were significantly decreased, compared with those of normal subjects (3.4 +/- 0.9 microgram/dl, mean +/- SD. vs. 9.0 +/- 1.5 microgram/dl, p less than 0.01 and 87 +/- 27 ng/dl vs. 153 +/- 37 ng/dl, p less than 0.01, respectively). FT4I was lower than the normal range in all but one (5.3 +/- 1.5 vs. 8.9 +/- 1.6, p less than 0.01), whereas FT3I was all in the normal range and of no significant difference from the normal control (132 +/- 22 vs. 148 +/- 25). Serum TSH concentrations in TBG deficiency were all in the normal range (1.0-4.2 muU/ml) and the maximum TSH increments following TRH 500 microgram iv were 8.9 +/- 2.0 muU/ml and of no significant difference from the normal control (10.2 +/- 4.5 muU/ml). These results indicate that the euthyroid state in familial TBG deficiency is more clearly defined by TRH-test and the normal response to TRH in familial TBG deficiency is presumably under the control of the serum free T3 level rather than the serum free T4 level.     

Effect of pentagastrin on adrenocorticotropin hormone and thyroid-stimulating hormone release in normal subjects

The possible role of gastrin on TSH, ACTH and cortisol secretion was evaluated by intravenous administration of pentagastrin, the carboxyl-terminal tetrapeptide of gastrin (0.5 microgram/kg b.w.) into 12 healthy subjects. Pentagastrin produced a significant rise in plasma ACTH and cortisol levels but did not alter TSH basal release. These preliminary results suggest that gastrin can influence basal activity of ACTH-cortisol axis. However, further investigation is required to determine its physiological role and mechanisms of action.     

Effects of pargyline on hypothalamic biogenic amines and serum prolactin. LH and TSH in male rats.

The time course effects of pargyline on hypothalamic biogenic amines and serum prolactin (PRL), LH and TSH were studied in adult male rats. The rats were killed at intervals of 1–6 hrs after pargyline injection. Hypothalamic dopamine (DA) rose 79% by 1 hr and was 41% above “0” time by 6 hrs. Norepinephrine (NE) increased 31% by 1 hr and remained at about this level through 6 hrs, whereas serotonin (5HT) increased from 42% by 1 hr and to 95% by 6 hrs. Serum PRL LH and TSH fell significantly during the first 2 hrs, but all had returned to pretreatment values by 4 hrs. Serum PRL was about 4-fold above pretreatment values by 6 hrs, but LH and TSH remained at pretreatment levels. Stimulation by pargyline of PRL release was potentiated by Lilly compound 110140, a serotonin reuptake inhibitor, and blocked by parachlorophenylalanine, a serotonin synthesis inhibitor. These results suggest that the inhibitory effects of pargyline on PRL, LH, and TSH release during the first 2 hrs were associated mainly with a rapid increase in DA, and subsequent elevation of PRL release was related to the increase in 5HT. Return of serum LH and TSH to pretreatment levels at 4 and 6 hrs appeared to be associated mainly with the decrease in DA and perhaps to elevated NE levels. These results suggest that changes in relative concentrations of hypothalamic amines are related to differential release of PRL, LH and TSH.     

The role of bombesin in regulating thyrotropin secretion in rats. In vivo studies

The effect of bombesin administered intravenously or intracerebroventricularly was investigated in 66 male Sprague-Dawley rats. Blood for determinations was sampled by cannulation of right heart auricle before and four times after the administration of bombesin. It was found that bombesin administered intravenously at doses of 0.5 and 5 micrograms/kg caused an elevation of blood plasma TSH. When administered intracerebroventricularly at doses of 0.1 and 1 microgram per animal bombesin did not change blood plasma TSH concentration; administered by the same way at a dose of 1 um per rat it lowered, however, the response of TSH to TRH.     

The use of intramuscularly administered methyl-TRH to evaluate the pituitary-thyroid axis.

The present study was carried out to evaluate the effectiveness of intramuscular administration of methyl-TRH, a potent analogue of thyrotropin-releasing hormone, for assessing pituitary reserve of TSH and prolactin and for distinguishing euthyroid, hypothyroid and hyperthyroid individuals. Serum samples were taken for 24 hours after intramuscular injection of methyl-TRH, 200 microgram, in 19 euthyroid subjects, 9 hypothyroid men and 9 hyperthyroid men. The mean serum prolactin and TSH concentrations were significantly elevated over baseline levels at 30 min in the euthyroid individuals and remained elevated for 3 to 4 hours. The serum TSH, T3 and T4 responses after intramuscular methyl-TRH in euthyroid subjects were clearly distinguishable from those of hyperthyroid and hypothyroid patients. Significant elevation of the serum T3 and T4 concentrations at 24 hours after intramuscular injection of methyl-TRH shows the sustained effect of this TRH analogue in euthyroid subjects.     

SMS 201-995 and thyroid function in acromegaly: acute, intermediate and long-term effects.

The acute (TRH-stimulation test), intermediate (0-6 days administration), and long-term (0-30 months administration) effects of SMS 201-995 (octreotide) treatment on thyroid function were studied. Subcutaneous injection of 100 micrograms SMS 201-995 one hour before 200 micrograms TRH intravenously reduced serum TSH response area by more than 50% in 8 healthy volunteers. After 3 days of continuous subcutaneous infusion (CSI) of SMS 201-995 in 9 acromegalic patients (100 micrograms/24 h) a slight but significant decrease in serum total triiodothyronine (TT3) and a concomitant increase in serum TSH were demonstrated, indicating an initial inhibitory effect on peripheral deiodination of thyroxine. After a further 3 days treatment serum T3 and TSH had returned to prevalues. Six of the nine acromegalics were treated with SMS 201-995 (100-1500 micrograms/24 h) and admitted for diurnal hormone profiles on 13 occasions over 30 months. Apart from a barely significant increase in serum TSH, no changes in thyroid function were noted. The study was especially designed to detect minute changes over time in thyroid hormones. The only long-term effect of SMS 201-995 was the barely significant clinically irrelevant increase in serum TSH, possibly caused by a slight inhibition of peripheral deiodination of thyroxine.     

The relationship of decreased serum thyrotropin and increased colonic temperature in rats exposed to microwaves

Although decreased serum thyrotropin (TSH) concentration has been found to be part of the endocrine response pattern in rats exposed to microwaves and other stimuli, the response of individual endocrine organs was not activated simultaneously by a given irradiance. Therefore, analytical evaluation of the function of endocrine organs individually as well as collectively is required to characterize the extent of biological involvement in microwave exposure. We have studied the changes in TSH concentration in unanesthetized rats exposed to 2.45 GHz amplitude modulated (120 Hz) microwaves in the far field for 2 and 4 h, between 0 and 55 mW/cm2, and from 1 to 10 times to demonstrate any possible cumulation, acclimation, or sensitization process. Ether inhalation was administered to test the responsiveness of TSH in groups of rats that failed to respond to microwave exposure by lowering TSH concentration. In addition, groups of rats were sampled 24 h after microwave exposure to test the persistency of the microwave effect on serum TSH concentration. Results showed that TSH concentration decreased in rats after microwave exposure. Influence of microwave exposure on serum TSH concentration was independent of the number of exposures indicating absence of cumulation, acclimation, or sensitization. The microwave effect on serum TSH could be dependent on duration of exposure. Decreased TSH concentration was usually accompanied by increased colonic temperature. For 4-h exposure, the lowest irradiance was 20 mW/cm2 or a 0.3 degree C increase in colonic temperature independent of the number of exposures. For 2-h exposure, the lowest irradiance was 30 mW/cm2 or a 1.1 degree C increase in colonic temperature regardless of the number of exposures. All the rats exposed at 10 mW/cm2 for 2 h had a lower TSH concentration than those of sham-exposed rats. Occasionally, significant reduction in TSH concentration could not be found in rats exposed to 20 or 25 mW/cm2 for 2 h. None of the rats exposed at an irradiance lower than 10 mW/cm2 had any change in TSH concentration. Failure of change in TSH concentration in response to microwave exposure was not a reflection of a deficiency since these rats responded to ether inhalation by lowering their TSH concentration. The effect of microwave exposure on TSH concentration was not persistent after exposure. The relation between TSH concentration and colonic temperature was curvilinear (exponential). From these results, two mechanisms and their implications for man were discussed.(ABSTRACT TRUNCATED AT 400 WORDS)