Injection Of Thyrotropin Research Articles

TRH reverses the ECG and EEG ischemic changes induced by massive hemorrhage in rats

In a rat model of volume-controlled hemorrhagic shock causing the death of all saline-treated animals within 30 min of treatment, the intravenous bolus injection of thyrotropin- releasing hormone tartrate (TRH-T) at the dose of 4 mg/kg induced the prompt and sustained disappearance of the ECG and EEG signs of heart and brain ischemia, along with the reversal of hypotension and respiratory depression and with 100% survival rate at the end of the 2 h observation period. These data confirm that, in a pre-terminal condition induced by massive hemorrhage, timely treatment with TRH-T will restore heart and brain perfusion to levels compatible with survival and with functional recovery from ischemia and maintain it at those levels for some hours.

The activity of the thyroid glands in relation to genetic differences in wool production

Twelve adult castrate male Merino sheep from each of two flocks, genetically different in their capacity for clean wool production, were allocated to a high (H: 0.81 kg digestible dry matter day-1; 26 g N day-1) or low dietary regime (L: 0.42 kg digestible dry matter day-1; 9.5 g N day-1). The sheep weighed 47 kg (s.e. =0.8) at the start of the experiment, with sheep from the two genetic groups having similar average liveweights. The dietary treatments were imposed for between 4 and 10 weeks before eight samples of venous blood were collected from each sheep during 24 h. Each sheep was then injected with thyroid stimulating hormone (TSH), (1.25 unit/sheep) before seven samples of blood were collected during the following 24 h. The plasma from these blood samples was assayed for total thyroxine (T4) and tri-iodothyronine (T3). There were no significant differences between the flocks in either T3 or T4 before or after the injection of TSH. We concluded that differences in the activity of the thyroid gland were not necessary for the establishment of genetic variation in the rate of wool growth. The circulating levels of both T4 and T3 were greater in the sheep receiving the H dietary regime (T4: 81.4 v. 55.8 nmol L-1; P<0.5 and T3: 1.8 v. 1.0 nmol L-1; P<0.05). These differences were maintained after the injection of TSH, which approximately doubled the pre-injection levels of T4 in plasma 9-10 h after the injection. The levels of T3 also increased after the injection, reaching a maximum which was 2.3 times the average pre-injection concentration after 4-5 h.

Thyroid Function in Heifers Measured by Hormone Levels before and after Injection of Thyrotropin Releasing Hormone

Thyroid Function in Heifers Measured by Hormone Levels before and after Injection of Thyrotropin Releasing Hormone

Thyroid Function in Heifers Measured by Hormone Levels before and after Injection of Thyrotropin Releasing Hormone

Abstract Thyroid hormone levels before and after thyrotropin releasing hormone (TRH) injection were compared at four different stages in relation to parturition in nine heifers. Basal thyroxine (T4) levels were similar before conception and two weeks before calving, but the T4 responses to TRH were reduced near parturition. Hormone levels and responses were low 2 weeks as well as three months after parturition. Both basal levels of T3 and T3 responses to TRH were low near parturition. Three months after parturition both basal level and TRH responses were comparable to those observed before conception. Low basal levels of thyroid hormones near parturition were not associated with an increased disappearance rate. Reduced thyroid secretion activity during early lactation must be the main explanation for the low thyroid hormone levels seen at this stage.

Effects of bovine TSH on the tissue thyroxine level and metamorphosis in prometamorphic flounder larvae

Bovine thyroid-stimulating hormone (TSH) was microinjected (0.2 microliter/fish) into prometamorphic flounder larvae and the effects on metamorphosis as well as the tissue thyroxine (T4) and triiodothyronine (T3) levels were studied. After a single injection of TSH (5 mIU/g), the tissue T4 concentration increased markedly after 5 hr, reached a peak after 10 hr, and decreased subsequently. T4 concentration after 24 hr was still higher than in saline-injected fish but returned to the control level 48 hr after the injection. On the other hand, tissue T3 concentration was kept lower than the detectable level (0.2 ng/g) throughout the experimental period of 72 hr after a single injection of TSH (5 mIU/g). TSH treatment also accelerated the process of metamorphic climax, such as shortening of the second fin ray and eye migration. These results suggest that an increased secretion of TSH from the pituitary stimulates the thyroid, resulting in a surge of the tissue T4 concentration which induces the climax of the flounder larvae.

Effect of Thyroidectomy of Immature Male Chickens on Circulating Thyroid Hormones and on Response to Thyroid-Stimulating Hormone and Chronic Cold Exposure

Previous studies in the author’s laboratory established that thyroidectomized (Tx) immature male chickens had significant levels of circulating thyroid hormones, and it was proposed that extrathyroidal tissue might be present. Three experiments were conducted to further investigate this possibility. In all experiments, thyroid glands were removed surgically at 3 wk of age. In the first experiment, birds were kept until 20 wk of age. It was found that only triiodothyronine levels were reduced significantly in the Tx birds. In the second experiment, Tx as well as sham-operated control groups received a single iv injection of bovine thyroid-stimulating hormone (TSH) to determine if extrathyroidal tissue in Tx birds would respond to exogenous TSH. It was found that circulating thyroxine (T4) concentrations in sham-operated control birds, but not Tx birds, were increased following TSH injection. In the third experiment, Tx and sham-operated birds were exposed chronically to cold (7 C), and only circulating T4 was found to be elevated in both groups. It was concluded that extrathyroidal tissue in Tx birds does not respond to TSH.

Effect of fatty acid administration on plasma thyroid hormones in the domestic fowl

In birds a severe stress is associated with a reduction in concentrations of plasma thyroxine. Studies in man and the rat have demonstrated that severe illness is associated with an increase in serum concentrations of free fatty acids, notably oleic acid, and that they are associated with a reduction in concentrations of serum thyroxine (T 4) and/or triiodothyronine (T 3). Since stress is associated with increased fatty acids in birds, we have, in the present study, examined the role of oleic acid and another polyunsaturated fatty acid, arachidonic acid, on thyroid function tests (plasma thyroxine, triiodothyronine, and T 3 resin uptake (RT 3U) index) and on the thyroidal response to exogenous thyroid-stimulating hormone (TSH) in the domestic fowl. In the first study we observed that the iv administration of arachidonic (10 mg/kg) or oleic acid (15 mg/kg) to groups of 10-week-old cockerels (six per group) was associated with a significant reduction in concentrations of plasma T 4, whereas there was little change in saline-injected controls. However, administration of fatty acids to chickens was not associated with a significant change in RT 3U index or in the levels of plasma T 3. In the second study, groups of animals ( n = 6) were injected with bovine TSH (0.5 IU/kg, im) or saline 2.5 hr after the fatty acid injection and blood samples were obtained at −2.5 to 24 hr after the TSH injection. A similar progressive increase in serum T 4 was observed for the three groups studied whereas there was little change in the concentrations of plasma T 3. In conclusion, injection of unsaturated fatty acids in the chicken is associated with a significant reduction in the concentrations of plasma T 4 and the fall is not due to a compromise in the thyroidal response to TSH or to an alteration in the binding of thyroid hormones to their plasma binding proteins.

Variation in thyroid response to thyroid-stimulating hormone in juvenile coho salmon ( Oncorhynchus kisutch)

Changes in the circulating levels of thyroid hormones measured by radioimmunoassay in yearling coho salmon in response to injection of bovine thyroid-stimulating hormone (TSH) were evaluated from January through August. Doses of TSH ranging from 0.2 to 6.4 μg/g body wt were ineffective in stimulating T 4 in January and at one time in April. Responses to TSH injection at this dose range were observed beginning in February and continuing through August. The minimal effective dose of TSH was either 0.2 or 0.4 μg/g from May through August. The dose-response relationships of bovine and coho salmon TSH were compared and found to be similar. The time course of response of juvenile salmon to either bovine TSH or partially purified salmon TSH was found to be similar in January, May, and August, although the magnitude of the response differed at these different times. It is concluded that the increase in thyroid response to TSH may play a part in the onset of the increase in circulating T 4 at the time of smoltification, but such changes in sensitivity do not explain the decrease in circulating T 4 at the completion of smoltification.

Bimodal variations in subcellular structures of rat thyroid follicular cells during 24 hours: fine structural and morphometric studies.

To clarify 24-hr variations in rat thyroid follicular cells under physiological conditions, their subcellular structures were examined at six evenly spaced times during 24 hr by using a morphometric technique. The volume, surface, and numerical densities of subcellular structures varied distinctly over each 24-hr period, with a bimodal pattern. The cellular and nuclear volumes varied also bimodally over 24 hr. A decrease in the surface density of the apical plasmalemma at 1200 and 0000 hr coincided with an increase in volume density of cytoplasmic granules representing colloid droplets and dense bodies. Most granules (colloid droplets) appearing at these times were reduced in electron density. At other times, especially at 1600 and 0400 hr, morphometric parameters of rough endoplasmic reticulum (rER), Golgi complex, and subapical vesicles were prominently increased, although values for rER did not peak at 1600 hr. At these times, the volume densities of cytoplasmic granules, most of which were heterogeneous and of homogeneous electron density, were decreased. These findings coincided with immediate and subsequent reactions of follicular cells after injection of thyroid-stimulating hormone (TSH). From the evidence, it seems likely that variations in follicular cells over a 24-hr period reflect variations in blood TSH concentration. The total membrane areas of membrane components in follicular cells were calculated from the morphometric measurements. These areas fluctuated unimodally during 24 hr over a 65% range. This suggests that the membranes in follicular cells are subjected to cyclic degradation and regeneration during each 24-hr period.

The nature of thyrotropin stimulation of thyroid function in Japanese quail: Prolonged thyrotropin exposure is necessary to increase thyroidal 125I uptake

1. 1. Single injections of thyrotropin (TSH) increase serum T 4 and thyroidal 32P uptake but not thyroidal 125I uptake regardless of dosage, exposure time or age. Chronic TSH exposure, with 3 or more days of injection, does increase thyroidal 125I uptake. 2. 2. Studies using iodine (I) supplementation indicated that the increased thyroidal radioiodine uptakes seen with chronic TSH administration were not due to an I deficiency in the thyroid resulting from high hormone release. 3. 3. Labeled and unlabeled experiments comparing the effects of single vs. multiple injections of TSH were used to describe the effects of TSH on hormone release, hormone production and thyroidal I uptake.

Genetics of heat tolerance and thyroid function in Athens-Canadian randombred chickens

Five experiments were conducted to assess the genetic variation in thyroid function (T3, T4), body weight and heat stress survival time in chickens. Thyroxine (T4) levels were found to be elevated in response to 4 and 8 μg bovine thyroid stimulating hormone (TSH) in experiment I. In experiment II, 4 μg of TSH was injected into chickens from 30 sire families of the Athens-Canadian Randombred population. The heritability of T4 levels after TSH injection was high. In experiment III, families identified as having innate high or low T4 levels after TSH injection and a group of control birds were subjected to a heat Stressor of 50 °C for up to 240 min at six weeks of age and heat stress survival time was studied. The groups did not differ from each other in heat stress survival time. Experiment IV was similar to experiment I except triiodothyronine (T3) was also measured after TSH injection. Both T4 and T3 levels after TSH injection were moderately heritable. In experiment V birds were reared to six weeks of age and heritability calculated for body weight, T4, T3, and heat stress survival time. Heritabilities were high for body weight, moderate for T4 and heat stress survival time, and low for T3. Phenotypic correlations were significant and negative for heat stress survival time with body weight and T4, and for body weight with T3 after TSH. Significant positive correlations were found for T4 with T3 after TSH and also T4 and body weight. Analysis of genetic correlations suggested that none of the traits studied would be an adequate selection parameter for achieving heat tolerance without reducing body weight.

Effects of TSH, TRH, LH and LHRH on thermoregulation and food and water intake in the rat.

The effects of administration of thyroid-stimulating hormone (TSH), thyrotropin-releasing hormone (TRH), luteinizing hormone (LH) or luteinizing hormone-releasing hormone (LHRH) into the lateral cerebral ventricle on thermoregulation and food and water intake were assessed in rats. Intracerebroventricular, but not intraperitoneal, injection of TSH, LH or LHRH produced hypothermia in rats at ambient temperatures of both 8 and 22 degrees C. The hypothermia in response to TSH injection was due to both decreased metabolic heat production and increased heat loss (cutaneous vasodilatation). The hypothermia in response to either LH or LHRH was due solely to decreased metabolic heat production. There was no change in respiratory evaporative heat loss in response to TSH, LH or LHRH injection. Furthermore, food but not water intake was greatly reduced following an intracerebroventricular injection of TSH or TRH in rats. On the other hand, intracerebroventricular administration of LH, but not LHRH, caused an increase in relative water intake (or water/food) in rats. However, intracerebroventricular administration of LH or LHRH had an insignificant effect on food intake. The data indicate that, in addition to their hormone actions, TSH, LH and their releasing hormones act through a central mechanism to influence some of the physiological or behavioral functions.

Plasma iodothyronine levels in lambs during the perinatal period: influence of thyrotropin injection.

Plasma thyroxine (T4) and triiodothyronine (T3) levels were measured in 7 pregnant ewes and their 9 chronically cannulated foetuses during the last 37 days of gestation and the first 5 days after parturition. The highest plasma T4 and T3 levels were measured in lambs during the hours following parturition. In 7 chronically cannulated 139-day old foetal lambs, the intravenous injection of ovine thyrotropin (oTSH; 7 mU per foetus) induced a significantly more intense increase in plasma T4 and T3 levels than that observed after the same dose of oTSH in seven 130-day old foetuses. In newborn lambs, the increase in plasma T4 levels after oTSH injection (3.5 mU per kg body weight) was not different in 8-hour old and 36-hour old animals, but was more intense at 120 h after birth than at 8 or 36 h after birth. The rise in plasma T3 levels after oTSH increased with age at 8, 36 and 120 h following birth. Plasma T4 and T3 measurements made in the same lambs before and after birth confirmed the fragmentary values obtained in foetal and newborn lambs in other previous studies. The rise in plasma iodothyronine levels after TSH injection in lambs increased at the end of gestation and the beginning of neonatal life, except during the first hours after delivery when these levels were high.

Mitotic rate of rat thyroid follicular cells in vivo in response to a single injection of thyrotropin (TSH).

The mitotic rate of thyroid follicular cells was assessed by a stathmokinetic method at intervals from 15 min to 24 hr after a single injection of 1 iu/kg of thyrotropin (TSH). The mitotic rate was increased 15 min after TSH and remained elevated for 3 hr. Two further peaks of mitotic activity were present at 9 hr and 24 hr after TSH. Serum TSH concentrations were increased from 5 min to 3 hr with a maximum at 1 hr.

Thyrotropin-releasing hormone and amphetamine produce different patterns of behavioral excitation in rats

We compared the arousal and hyperactivity produced by intraperitoneal (i.p) injections of thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH 2; 10, 20, 30 and 60 mg/kg) and 0.3 and 2 mg/kg d-amphetamine (low and moderate amph., respectively) by measuring the occurrence of discrete behavioral items with a behavioral sampling and scoring method. To minimize extraneous variables affecting activity, rats were caged singly inside isolated observation chambers and tested in the daytime after a 2.5 h period of habituation. Under these conditions, vehicle (0.9% NaCl)-treated rats were inactive and either rested or slept through 80% of all time samples taken in the hour after injection. Both TRH and amph. produces significant arousal from sleeping, but TRH, at all doses tested, produced less arousal than moderate amph. and a pattern of behavioral responses which differed from both low and moderate amph. Moderate amph. produced marked increases in forward locomotion and rearing, but low amph. and TRH did not. Both TRH and low amph. increased grooming (perhaps simply by increasing wakefulness), but TRH failed to increase sniffing, a cardinal feature of amph.-induced excitement. Unlike amph., TRH produced wet-dog shakes, piloerection, tail elevation and teeth chattering. Both mod. amph. and TRH significantly produced increased activity when compared to controls as assessed with photocell counts, though the amph. effect was more robust. The lack of arousal after i.p. injections of thyroid-stimulating hormone (10 I.U./kg) or melanocyte-stimulating hormone release-inhibiting factor (Pro-Leu-Gly-NH 2; 60 mg/kg) is evidence that TRH-induced arousal is neither mediated by activation of pitupituitary-thyroid axis nor by a non-specific effect of tripeptides generally.

Quantitative modulation of thyroid iodide peroxidase by thyroid stimulating hormone

The activity of rat thyroid iodide peroxidase fell to 8% of the normal value 48 hours after hypophysectomy. Rats given injections of thyroid stimulating hormone manifested an enzyme activity indistinguishable from that of the sham-operated animals. Cycloheximide prevented the thyroid stimulating hormone-induced restoration of the enzyme activity. The incorporation of 14C-leucine into the thyroid gland decreased gradually and reached two thirds of the sham-operated group by 48 hours after hypophysectomy. Thyroid stimulating hormone administration prevented this decrease, as observed for iodide peroxidase activity. Thyroidal RNA contents decreased also in hypophysectomized rats, thyroid stimulating hormone treatment prevented the reduction of RNA contents and no significant change was observed in thyroidal DNA contents. These data are consistent with the idea that protein biosynthesis is involved in thyroid stimulating hormone regulation of thyroidal iodide peroxidase and that the life span of the peroxidase is less than 48 hours.

Effects of Hypophysectomy and TSH on Thyroidal Fucokinase in Rats

SummaryThe purpose of the present investigation was to determine whether rat thyroid fucokinase is responsive to hypophysectomy and to administration of thyroid stimulating hormone (TSH). Prior to measurements of fucokinase activity in thyroid extracts, any potential low-molecular-weight effectors were removed from the extracts by a molecular sieving procedure. With this procedure, thyroid fucokinase activity in hypo-physectomized rats was found to be 55% lower than in intact rats. Injections (i.p.) of TSH into the hypophysectomized rats, however, restored the activity lost upon hypophysectomy to levels that were not significantly different from those of intact animals. Also, when intact rats were given injections (i.p.) of TSH, thyroid fucokinase activity was elevated significantly above that found in intact animals given injections of carrier only.

Administration of thyrotropin releasing hormone (TRH) to rats releases dopamine in n. accumbens but not n. caudatus

Bilateral injection of thyrotropin releasing hormone (TRH; 10 μg) into the n. accumbens of rats produced a short-lasting increase in co-ordinated locomotor activity and behavioural changes similar to those produced by injection of dopamine at this site. These effects were potentiated and prolonged by pretreatment with tranylcypromine (5 mg/kg i.p.). Injection of haloperidol (2.5 μg bilaterally) into the n. accumbens blocked the behavioural changes produced by intra-accumbens injection of TRH (10 μg bilaterally. 30min after tranylcypromine 5 mg/kg i.p.). Destruction of the presynaptic dopamine terminals with 6-hydroxydopamine (8 μg bilaterally) abolished the effects of intra-accumbens injection of TRH (10 μg bilaterally) in either untreated or tranylcypromine pretreated rats. This inhibition was not due to non-specific damage to post-synaptic dopamine receptors since these rats showed a normal locomotor response to intra-accumbens injection of dopamine (5 μg bilaterally. 30min after tranylcypromine 5 mg/kg). These results suggest that TRH is acting by release of dopamine. Peripheral injection of TRH (20 mg/kg) produced behavioural changes similar to those observed after central administration of this drug. Although these effects were not enhanced by pretreatment with tranylcypromine (5 mg/kg. 30min before TRH), they were blocked by peripheral injection of haloperidol (1 mg/kg). Injection of thyroid stimulating hormone (TSH: 20 mg/kg i.p.) produced no behavioural changes suggesting that peripherally injected TRH is not acting by release of TSH. Injection of TRH (20 mg/kg i.p.) to unilateral nigro-striatal lesioned rats failed to induce circling. Furthermore pretreatment with TRH (2 mg/kg i.p.) did not enhance the turning produced by methamphetamine (0.5 mg/kg) 3 hr later in tranylcypromine-treated animals. This evidence suggests that in contrast to its effects in the n. accumbens TRH is unable to release dopamine in the n. caudatus.

Behavioural, electrocortical and body temperature effects after intracerebral infusion of TRH in fowls

In fowls TRH given into the III cerebral ventricle (0.25–5 μg) produced intense behavioural stimulation, electrocortical desynchronization and a slight increase in body temperature. In particular, an intense pattern of stereotyped head-neck movements, increase in locomotor activity, repeated and preening, vocalization, erection of the tail feathers and occasionally ‘escape responses’ were observed. This picture lasted for about 30 min and was followed by slight behavioural sedation during which stereotypies continued to occur but to a lesser extent. Similar increases in locomotor activity and stereotypies were evoked by infusing TRH into the hypothalamus whereas the unilateral microinfusion into the n. basalis or the n. mesencephalicus profundus, homologous to the mammalian striatum and s. nigra respectively, produced very intense stereotyped head-neck movements, wet-dog syndrome and vocalization. TRH given into the other areas of the brain (e.g. hyperstriatum, neostriatum, olfactory ventricle, eminentia basalis and lateral part of the mesencephalon) lacked effects on behaviour and body temperature. The effects of intraventricular infusion of TRH were antagonized by prior administration of haloperidol and spiperone whereas antagonists at α and β-adrenoceptors and at 5-HT receptors were ineffective. In addition, TRH reversed sedation induced by intraventricular α-methyl-p-tyrosine. Behavioural and body temperature effects of TRH were independent of its endocrine properties since these were not observed after systemic or intracerebroventricular injection of thyrotropin, triidothyronine and thyroxine. The increase in body temperature evoked by intracerebroventricular injection of TRH was due to activation of heat production and decrease in thermodispersive mechanisms.

Stimulant action of thyrotropin releasing hormone on cat spinal cord

Thyrotropin releasing hormone (TRH) produced a rapid dose related elevation of muscle tonus accompanied by tremor and shivering-like movements in cats. This stimulant action of TRH also occurred in decerebrate cats and cats which had undergone spinal cord transection at the level of the first cervical vertebra. Recordings froir spinal cord ventral roots indicated that TRH induced a pronounced increase in spontaneous motor neuron action potentials. No such stimulation of muscle activity was produced by injections of thyrotropin (TSH), triiodothyronine (T 3), deamidated TRH, or the constituent amino acids of TRH, pyroglutamic acid, histidine, and proline amide. Results suggest that TRH can act directly on the spinal cord to stimulate muscle activity via a nonendocrine mechanism.