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Biomedical subjects

P Langer

Publications and source records attributed to P Langer.

At least 163 records · Page 9Linked to original sources

Changes in adenylate cyclase activity in rat pituitary after TRH and T3 injection in vivo.

Increased activity of adenylate cyclase in whole anterior pituitary was repeatedly found in groups of 3-6 adult male rats 5 min after iv injection of 10, 100 and 200 nmol of TRH kg-1. After the administration of 100 nmol TRH kg-1 the activity of adenylate cyclase was significantly increased at 2, 5, 10 and 30 min with a peak level at 5 min, while at 60 min the values did not differ from controls. The level of TSH in serum was significantly increased in all TRH injected groups with a peak value at 10 min, while no dose-response relationship was found at 5 min. Finally, the activity of adenylate cyclase was significantly decreased in animals injected with 20 nmol of L-triiodothyronine kg-1 180 min before sacrifice, the decrease being not overcome by 100 nmol TRH kg-1 injected 5 min before sacrifice.

Adenylyl Cyclases↗

In vitro effect of TRH on adenylate cyclase and cAMP in rat anterior pituitary and on TSH and PRL release into incubation medium.

Rat anterior pituitaries were incubated for 20 min with 1, 5 or 20 nmol TRH ml-1 and cAMP was measured in the homogenate of pituitary tissue after incubation, while TSH and PRL release into the medium was estimated with the aid of specific radioimmunoassay. In a similar experiment the activity of adenylate cyclase in pituitary homogenates was measured after the incubation with 0.5, 1.0 or 5.0 nmol TRH ml-1. Significant increase of TSH and PRL in the medium was found after 5 and 20 nmol TRH ml-1, while cAMP was significantly increased after 20 nmol TRH ml-1 only. The activity of adenylate cyclase was significantly increased after all doses of TRH used. In general, these findings are consistent with current views on the effect of hypothalamic hormones via adenylate cyclase - cAMP system and show that the responsiveness and sensitivity of an in vitro system using whole pituitaries appears to be less that of in vivo system.

Adenylyl Cyclases↗

Acute effect of salicylate on T4 and T3 levels in plasma and their excretion by bile in rats.

Male Wistar rats weighing about 400 g were anaesthetized with pentobarbiturate (40 mg kg-1) i.p. and thin polyethylene tubings were inserted in left femoral artery and vein as well as in a bile duct. Blood samples were taken at 30-60 min intervals for 6 h. The total bile was collected to pre-weighed glass vials. With the aid of radioimmunoassay the level of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) was estimated in plasma and the total excretion of these compounds by bile was measured after the incubation of bile aliquots with beta-glucuronidase-arylsulphatase. After i.v. injection of sodium salicylate (S; 80 mg kg-1) a significant decrease of T4 and T3 in plasma was found compared either to the initial level found in the same animals or to that found in controls not injected with S. Total excretion of bile was increased within 2 h after the administration of S. Under these conditions, the excretion of T4 was increased, while that of T3 was decreased. It is suggested that the effect of salicylate under the experimental conditions used consists of: 1. displacement of iodothyronines from plasma protein binding; 2. increased bile excretion (during the initial period after the administration of S) presumably due to the increased blood flow through the liver.

Animals↗

Studies on the effect of pentobarbiturate, ether and heparin on plasma thyroxine level in rats.

In groups of 9 to 20 adult male rats decapitated at 0, 15 or 60 min after i.p. injection of saline or at the same intervals after 2 min exposure to ether no differences in plasma thyroxine level were found. In groups of 5-6 animals a significant decrease of thyroxine level in plasma was observed at 30 min after i.p. injection of pentobarbiturate (40 mg kg-1) and unsignificant decrease after 800 and 2400 U heparin i.p. per animal. Finally, in 58 animals a linear decrease of plasma thyroxine level was found during 480 min beginning from about 60th to 90th min after the onset of pentobarbiturate anaesthesia (40 mg kg-1 followed by 20 mg kg-1 every 60-90 min). It was concluded that the blood clotting preventive dose of heparin (i.e. 300 U per 400 g animal) presumably does not interfere with the level of thyroxine in plasma, while pentobarbiturate apparently results in a considerable decrease of that.

Anesthetics↗

Does a short-term draining of bile duct affect the plasma thyroxine level in rats?

In three groups of male rats weighing about 350 g and fed normal pelleted diet the left femoral artery and vein were cannulated under pentobarbiturate anesthesia and in samples of plasma obtained between 0 and 6 h after the injection of heparin the level of thyroxine (T4) was measured with the aid of specific radioimmunoassay. In addition, in Group A (22 animals) and C (17 animals) also the bile duct was cannulated and the total bile was collected into a flask for the same period. In addition, the animals of a Group C were thyroidectomized by electrocoagulation immediately before "O h". The Group B consisted of 18 sham-operated animals in which, in addition to the cannulation of blood vessels, only laparotomy and separation of bile duct without cannulation were made. In all groups a linear decline of plasma T4 level was found corresponding to a half-life of about 11 h. Since there were no significant differences in the slope of regression line between groups, it was concluded that the period of draining bile duct for 6 h was presumably too short to interfere significantly with the absorption of T4 in lower intestine and ileum and that the uniform decline of T4 level in plasma in all groups was presumably due to the effect of pentobarbiturate.

Animals↗

Short-term effect of acetylsalicylic acid analogue on pituitary-thyroid axis and plasma cortisol level in healthy human volunteers.

The effect of acetylsalicylic acid analogue (aloxiprinum; Superpyrin Spofa) administered perorally in a daily dose of 1 g per 10 kg body weight on serum levels of free thyroxine (FT4), total thyroxine (T4), triiodothyronine (T3), cortisol (F) and thyrotrophin (TSH) was studied in healthy human volunteers. In a first experiment the drug was administered for 3 days to 7 subjects, the total daily dose being divided into 4-5 aliquots, while the same total dose was administered within 4 h to another 8 subjects in a second experiment. In both experiments a highly significant increase of FT4 was found during the period of treatment, while the levels of other hormones i.e. (T3, T4, F and TSH) were decreased, in most cases significantly. After the withdrawal of the drug there was not only a return of all levels to the initial value, but in most cases an "overshoot" above this value was detected.

Adult↗

Lesions of some central nervous structures result in altered pituitary-thyroid response to acute decrease of blood thyroid hormone level.

Eight groups (3--6 animals each) of rats weighing 350--400 g were subjected to electrolytic lesions of various parts of habenular, thalamic and hypothalamic areas of brain. On the 6th day after the lesion the level of blood thyroid hormone was acutely decreased with the aid of isovolemic exchange transfusion (IET) of thyroid hormone free blood suspension. The level of thyroxine (T4) in plasma was measured before and during 180 min after IET with the aid of specific radioimmunoassay and the changes of its post-transfusion level were evaluated. It was found that in three groups of animals bearing large bilateral lesions either in lateral ventral thalamus or in a central inferior thalamus the response of T4 level during the post-transfusion period is similar to that found in intact control groups from previous experiments. This consists in an increase of T4 level nearly to the initial value within about 120--150 min after IET. In contrast, there was only a slight post-transfusion increase of T4 level in one group with small central lesion in medial superior thalamus and no increase in two groups bilaterally lesioned in habenular area and in another two groups lesioned either in a central part of dorsal hypothalamus or in a central dorsal part of ventral basal hypothalamus. It was concluded that some parts of brain may be involved in managing the appropriate response of pituitary-thyroid axis to acute decrease of thyroid hormone level, no plausible explanation of the mechanism ofthe observed phenomena being offered.

Animals↗

Changes of LH, TSH, GH, FSH and PRL in pituitaries and sera of rats after thyroidectomy and thyroxine treatment as studied by radioimmunoassay and disc electrophoresis.

Rat pituitary hormones (LH, TSH, GH, FSH and PRL) were located in polyacrylamide gels after the separation of rat pituitary homogenate with the aid of electrophoresis. Furthermore, the incorporation of 3H-glucosamine and 14C-leucine into various protein fractions of incubation media and pituitaries incubated for 6 h in vitro, homogenized and then subjected to disc electrophoresis was measured in six groups of rats: 1. control; 2. two weeks after thyroidectomy (Tx); 3.--6. two weeks after thyroidectomy and injected 20 micrograms L-thyroxine (T4) i.p. per animal at 6, 12, 24 and 48 h before sacrifice, respectively. A decrease of 14C-leucine incorporation into GH and PRL after thyroidectomy was found which was improved by T4 treatment. Moreover, an increase of 3H-glucosamine and 14C-leucine incorporation into TSH zone and origin zone was observed, the former presumably representing the extracted TSH and the latter consisting of unextracted portion of TSH, other hormones and unidentified proteins. Such increase was significantly less after T4 treatment. Finally, changes of radioimmunoassayable LH, TSH, GH, FSH and PRL in pituitaries and sera of analogous groups of rats, but consisting of another animals were measured. The content of TSH in the pituitary slightly increased after Tx, but increased further after T4 treatment. In contrast, the content of all other hormones in the pituitary decreased after Tx, while T4 treatment resulted in a stepwise increase. In plasma, a significant decrease of GH and PRL after Tx was found with no remarkable changes after T4 treatment. The level of LH and FSH was unchanged, while that of TSH increased significantly after Tx and sharply decreased to the original level as early as at 6 h after the injection of T4.

Animals↗

Acute decrease of blood thyroid hormone by isovolemic exchange transfusion as a stimulus for pulse TSH release and its modifications by CNS Lesions.

The level of thyroid hormone in blood has been acutely decreased by about 20--30% within 20 min with the aid of isovolemic exchange transfusion (IET) of thyroid hormone free blood cell suspension (THFBCS) in three groups of rats: (1) intact control (C); (2) median eminence (ME)-lesioned; (3) thalamus (TH)-lesioned. The levels of thyroxine (T4) and TSH were measured by specific radioimmunoassay (RIA) before the transfusion and for 180 min after that. The level of T4 increased to the initial value at about 120 min after IET in C and ME-lesioned rats, while in TH it remained decreased until 180 min. Furthermore, at the end of IET the level of TSH in C and ME-lesioned rats was about 2--3 time higher than the initial value and its continuous decrease was observed until 180 min. In contrast, in TH-lesioned rats the increase of TSH level was delayed, being significant at 60 min only. It was concluded that IET of THFBCS acts as a stimulus of acute TSH release which was remarkably inhibited in TH-lesioned animals. In addition, the destruction of most of the ME did not apparently influence this response, as shown by essentially similar data obtained in C and ME-lesioned rats.

Animals↗

Rapid disappearance of loading doses of thyroxine from blood and their excretion by the bile in rats.

The disappearance of loading doses of thyroxine (T4) (100-20 000 microng T4 iv per rat weighing about 400 g) was measured with the aid of new technique allowing frequent blood sampling with maintenance of isovolaemia in anaesthetized animals. It was found that as early as 2 min after the injection more than half of the administered dose disappeared from the blood, while after 300 min only about 2% of that remained in the plasma. The direct relationship between the administered dose of T4 and both the relative and absolute level of free dialyzable T4 as well as of per cent of T4 displaced from plasma by sodium salicylate in vivo was demonstrated. Moreover, it was found that about 60% of administratered T4 is excreted by the bile within 300 min irrespective of the dose given, about 15 and 50% of that being found in the small intestine after 15 and 180 min, respectively. When two loading doses of T4 were subsequently administered and labelled with different isotopes, the amount of T4 from the first dose excreted by the bile was proportional to the amount of T4 from a second dose administered 18 h later. From all these observations it was concluded that, in vivo, an effective system for removal of the loading doses of thyroxine from the blood exists, and is presumably located in rapidly equilibrating tissues, mainly in the liver. From this point of view it appears that plasma protein carriers play an important role in the whole body economy of thyroxine, namely by maintaining a certain level in the blood to cover the actual functional needs of peripheral tissues.

Animals↗

Comparison of preventive effect of T3 and T4 on thyroxine release from thyroid induced by endogeneous TSH after TRH injection.

Comparison of Preventive Effect of T3 and T4 on Thyroxine Release from Thyroid Induced by Endogenous TSH after TRH Injection. Endocrinologia Experimentalis 11, 91-98, 1977. The technique of frequent blood sampling through polyethylene tubings inserted into blood vessels while maintaining isovolemia was used in pentobarbiturate anaesthetized rats weighing 250--300 g. The animals were fed low iodine diet for 4 weeks and injected 125I- (5 microgram Ci per animal daily) for 6 days begining from 8th day before the experiment. The effect of 25 microgram TRH injected through a cannula inserted into carotid artery in cranial direction was evaluated as per cent increase of labelled thyroxine in plasma at 120 min after the injection compared to its level at 30 min. Moreover, the inhibitory effect of various doses of thyroxine (T4; 5, 20 and 80 nmol kg-1) and triiodothyronine (T3; 1.25 and 5 nmol kg-1) injected i.v. at the intervals of 10, 20, 30, 60 and 180 min prior to TRH was investigated. It was found that the effect was time dependent, being negligible after 10 or 20 min, while after 60 and 180 min the increase of labelled T4 after TRH was fully prevented by 20 and 80 nmol T4 kg-1 and by 5 nmol T3 kg-1. The other doses (i. e. 5 nmol T4 kg-1 and 1.25 nmol T3 kg-1) were without effect. Thus, T3 was found to be significantly more active than equimolar doses of T4.

Animals↗

Acute redistribution of thyroxine after the administration of univalent anions, salicylate, theophylline and barbiturates in rats.

Rats were injected with [125I]L-thyroxine (T4) ip 16 h before the experiment and samples of blood were frequently taken from polyethylene tubing inserted into the femoral artery in anaesthetized and heparin injected animals, isovolaemia being maintained. In each sample of plasma T4 counts per ml were estimated with the aid of paper chromatography. Rapid decrease of circulating T4 level was found at 20 min after iv injection of various compounds (thiocyanate, iodide, fluoroborate, theophylline and salicylate) and a dose-response relationship was established between such a decrease and the administered dose of salicylate (5-160 mg/400 g b.w.). A similar decrease was observed at 60 min after ip injection of some general anaesthetics (thio-, pento- and allo-barbiturate, urethane) or tranquilizers (Innovar-Vet). Finally, an incrase of T4 fractional disposal rate was found between 120 and 480 min after the administration of some of the above mentioned anaesthetics and this effect was abolished by the administration of thiocyanate. It was concluded that there are two different effects of drugs on the circulating T4 level: 1. the immediate effect resulting apparently from a decreased plasma protein binding; 2. the prolonged effect which presumably results from the increased turnover of T4 by peripheral tissues, the metabolic basis of which remains unexplained.

Animals↗