Bombesin inhibits thyrotrophin secretion in rats

1985 ◽  
Vol 108 (1) ◽  
pp. 79-84 ◽  
Author(s):  
Terunori Mitsuma ◽  
Tsuyoshi Nogimori ◽  
Masahiro Chaya
Keyword(s):  
Thyroid Hormone ◽  
Plasma Concentrations ◽  
Treated Group ◽  
Inhibitory Effect ◽  
Thyrotrophin Releasing Hormone ◽  
Tsh Secretion ◽  
The Central Nervous System ◽  
Thyroid Hormone Levels ◽  
Tsh Levels

Abstract. The effects of peripheral administration of bombesin on thyrotrophin-releasing hormone (TRH) and thvrotrophin (TSH) secretion in rats were studied. Bombesin (200 μg/kg) was injected iv, and the rats were serially decapitated. TRH, TSH and thyroid hormone were measured by radioimmunoassay. The hypothalamic immunoreactive TRH (ir-TRH) content increased significantly after bombesin injection, whereas plasma concentrations tended to decrease, but not significantly. Plasma TSH levels decreased significantly in a dose-related manner with a nadir at 40 min after the injection. Plasma thyroid hormone levels did not change significantly. Plasma ir-TRH and TSH responses to cold were inhibited by bombesin, but the plasma TSH response to TRH was not affected. In the pimozide- or para-chlorophenylalanine pre-treated group, the inhibitory effect of bombesin on TSH levels was prevented, but not in the l-Dopa- or 5-hydroxytryptophan pre-treated group. These drugs alone had no effect on plasma TSH levels in terms of the dose used. The inactivation of TRH immunoreactivity in plasma or hypothalamus in vitro after bombesin injection did not differ from that of the controls. These findings suggest that bombesin acts on the hypothalamus to inhibit TRH release, and that its effects are at least partially modified by amines of the central nervous system.

Effects of eledoisin on thyrotrophin secretion in rats

1985 ◽  
Vol 110 (1) ◽  
pp. 90-94
Author(s):  
Terunori Mitsuma ◽  
Tsuyoshi Nogimori ◽  
De Heng Sun ◽  
Masahiro Chaya
Keyword(s):  
Central Nervous System ◽  
Thyroid Hormone ◽  
Inhibitory Effect ◽  
Thyrotrophin Releasing Hormone ◽  
Tsh Secretion ◽  
Pretreated Group ◽  
The Central Nervous System ◽  
Thyroid Hormone Levels ◽  
Tsh Levels

Abstract. The effect of peripheral administration of eledoisin on thyrotrophin-releasing hormone (TRH) and thyrotrophin (TSH) secretion in rats were studied. Eledoisin (500 μg/kg) was injected iv, and the rats were serially decapitated. TRH, TSH and thyroid hormone were measured by radioimmunoassay. The hypothalamic immunoreactive TRH (ir-TRH) content increased significantly after eledoisin injection, whereas its plasma concentration tended to decrease, but not significantly. Plasma TSH levels decreased significantly in a dose-related manner with a nadir at 40 min after the injection. Plasma thyroid hormone levels did not change significantly. Plasma ir-TRH and TSH responses to cold were inhibited by eledoisin, but the plasma TSH response to TRH was not affected. In the pimozide- or para-chlorophenylalanine-pretreated group, the inhibitory effect of eledoisin on TSH levels was prevented, but not in the l-dopa- or 5-hydroxytryptophan-pretreated group. These drugs alone did not affect plasma TSH levels at the dose used. The inactivation of TRH immunoreactivity by plasma or hypothalamus in vitro after eledoisin injection did not differ from that of controls. These findings suggest that eledoisin acts on the hypothalamus to inhibit TRH release, and its effects are modified by amines of the central nervous system.

β-Neoendorphin inhibits thyrotrophin secretion in rats

1983 ◽  
Vol 104 (4) ◽  
pp. 437-442 ◽  
Author(s):  
Terunori Mitsuma ◽  
Tsuyoshi Nogimori
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Plasma Concentrations ◽  
Inhibitory Effect ◽  
Thyrotrophin Releasing Hormone ◽  
Specific Radioimmunoassay ◽  
Tsh Secretion ◽  
Pretreated Group ◽  
The Central Nervous System ◽  
Tsh Levels

Abstract. The effects of β-neoendorphin on thyrotrophin-releasing hormone (TRH) and thyrotrophin (TSH) secretion in rats were studied. β-neoendorphin (500 μg/kg) was injected iv, and the rats were decapitated serially. TRH, TSH, thyroxine (T4) and 3,3',5-triiodothyronine (T3) were measured by means of a specific radioimmunoassay for each. Hypothalamic immunoreactive TRH (ir-TRH) content increased significantly after β-neoendorphin injection, and plasma concentrations tended to decrease, but not significantly so. Plasma TSH levels decreased significantly in a dose-related manner with a nadir at 40 min. Plasma T4 and T3 levels did not change after the injection. Plasma ir-TRH and TSH responses to cold were significantly inhibited by β-neoendorphin, but the plasma TSH response to TRH was not. Naloxone partially prevented the inhibitory effect of β-neoendorphin on TSH release. In the haloperidol- or 5-hydroxytryptophan-pretreated group, the inhibitory effect of β-neoendorphin on TSH release was prevented, but not in the l-dopa- or para-chlorophenylalanine-pretreated group. These drugs alone did not affect plasma TSH levels at the dose used. These findings suggest that β-neoendorphin acts on the hypothalamus by inhibiting TRH release, which may be modified by amines of the central nervous system.

Dynorphin (1–13) effects on thyrotrophin-releasing hormone and thyrotrophin secretion in rats

1983 ◽  
Vol 103 (3) ◽  
pp. 359-364 ◽  
Author(s):  
Terunori Mitsuma ◽  
Tsuyoshi Nogimori
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Inhibitory Effect ◽  
Thyrotrophin Releasing Hormone ◽  
Releasing Hormone ◽  
Tsh Secretion ◽  
Pretreated Group ◽  
Basal Plasma ◽  
The Central Nervous System ◽  
Tsh Levels

Abstract. The effects of dynorphin (1-13) on thyrotrophin-releasing hormone (TRH) and thyrotrophin (TSH) secretion in rats were studied. Dynorphin (500 μg/kg) was injected iv, and the rats were serially decapitated. TRH and TSH, thyroxine (T4) and 3,3',5-triiodothyronine (T3) were measured by radioimmunoassay. The hypothalamic immunoreactive TRH did not change significantly after dynorphin injection. Basal plasma TSH levels significantly decreased in a dose-related manner with a nadir at 40 min after dynorphin injection. The effect of dynorphin on TSH release was partially prevented by naloxone. The plasma TSH response to cold was significantly inhibited by dynorphin. The plasma TSH response to TRH did not differ from that of the control. In the l-DOPA or 5-hydrotryptophan-pretreated group, the inhibitory effect of dynorphin on TSH release was prevented, but not in the haloperidolor para-chlorophenylalanine-pretreated group. These drugs alone did not affect plasma TSH levels. The plasma T4 and T3 levels did not change significantly after dynorphin injection. The findings suggest that dynorphin acts on the hypothalamus by inhibiting TRH release, which may be modified by amines of the central nervous system.

EFFECT OF THYROID STATUS ON THE THYROTROPHIN-RELEASING HORMONE-DEGRADING ACTIVITY OF RAT SERUM

1976 ◽  
Vol 71 (1) ◽  
pp. 13-19 ◽  
Author(s):  
N. WHITE ◽  
S. L. JEFFCOATE ◽  
E. C. GRIFFITHS ◽  
K. C. HOOPER
Keyword(s):  
Thyroid Hormone ◽  
Human Serum ◽  
Thyroid Function ◽  
Thyroid Status ◽  
Rat Serum ◽  
Thyrotrophin Releasing Hormone ◽  
Releasing Hormone ◽  
Tsh Levels

SUMMARY The TRH-degrading activity of rat serum in vitro is five times more potent than that of human serum. In rats, it is significantly reduced in hypothyroidism (thiouracil-induced) and significantly increased in hyperthyroidism (T3 or T4-induced). This suggests a possible role in the regulation of adenohypophysial-thyroid function which is probably, in turn, dependent on thyroid hormone, rather than TSH, levels.

Effects of intrathyroidal metabolism of thyroxine on thyroid hormone secretion: increased degradation of thyroxine in mouse thyroids stimulated chronically with thyrotrophin

1984 ◽  
Vol 105 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Ken Kubota ◽  
Hidemasa Uchimura ◽  
Tomoaki Mitsuhashi ◽  
Shoo Cheng Chiu ◽  
Nobuaki Kuzuya ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Secretion ◽  
Plasma Concentrations ◽  
Experimental Period ◽  
Physiological Significance ◽  
The Media ◽  
Bovine Tsh ◽  
Tsh Levels ◽  
Mouse Thyroid

Abstract. Mice were infused continuously with graded doses of bovine TSH (bTSH) and changes in plasma concentrations of bTSH and T4 were measured. Then mice infused with 100 mU TSH per day were sacrificed on days 0, 1, 3 and 5 and their thyroids were excised to determine in vitro secretion of T4, T3 and rT3 during 3 h of incubation. At the end of the incubation, thyroidal contents of T4, T3 and rT3 were also determined after pronase digestion. Plasma bTSH levels were increased on day 1 to a level of 110 μU/ml and remained unchanged thereafter. Plasma T4 concentrations increased approximately 2-fold on day 1, but decreased to initial levels on days 3 and 5. Changes in T4 secretion in vitro paralleled those in plasma T4 concentrations; T4 secretion increased 2-fold on day 1, and decreased to the pre-TSH levels on days 3 and 5. In contrast, T3 secretion increased throughout the experimental period. The T3/T4 ratio in thyroidal secretion in vitro was the same as that in thyroidal contents on days 0 and 1 of TSH infusion, but the former was significantly greater than the latter on days 3 and 5. PTU (5.9 × 10−5 m), a known inhibitor of T4 deiodination, added to the incubation media did not affect T4 secretion on days 0 and 1, but increased T4 secretion on days 3 and 5 to the level of day 1, but did not affect T3 secretion. In the presence of PTU, the T3/T4 ratio in thyroidal secretion did not differ from that in thyroidal contents throughout the experimental period. Secretion of rT3 was increased on days 3 and 5 and PTU augmented this increase. Thyroidal content of rT3 was much increased on days 3 and 5. In contrast, methimazole (10−3 m), which does not inhibit in vitro T4 deiodination, added to the incubation media did not affect T4, T3 and rT3 secretion in vitro. When [125I]T4 was added to the media and incubated with mouse thyroid, no labelled products of T4-deiodination were observed to appear in the media even in mice infused with TSH for 5 days. These results suggest that intrathyroidal metabolism of T4 has physiological significance in controlling thyroid hormone secretion at least in TSH-stimulated thyroids.

Deficient pulsatile thyrotropin secretion in the low-thyroid-hormone state of severe non-thyroidal illness

1994 ◽  
Vol 130 (2) ◽  
pp. 132-136 ◽  
Author(s):  
Nicola Custro ◽  
Vincenza Scafidi ◽  
Salvatore Gallo ◽  
Alberto Notarbartolo
Keyword(s):  
Thyroid Hormone ◽  
Healthy Subjects ◽  
Normal Subjects ◽  
Healthy Individuals ◽  
Circadian Variations ◽  
Tsh Secretion ◽  
Thyroid Hormone Levels ◽  
Rhythmic Change ◽  
Serum Tsh ◽  
Tsh Levels

Custro N, Scafidi V, Gallo S, Notarbartolo A. Deficient pulsatile thyrotropin secretion in the low-thyroid-hormone state of severe non-thyroidal illness. Eur J Endocrinol 1994;130:132–6. ISSN 0804–4643. Twenty-four-hour thyrotropin (TSH) profiles in eight severely ill patients were compared with those of six healthy subjects. The profiles were assessed using the cosinor method to evaluate circadian variations and using the Pulsar algorithm to analyze episodic secretion. In the normal subjects, the typical periodicity of TSH secretion showed a mean level in the rhythm (mesor) of 2.03 mU/l, The amplitude (half the extent of rhythmic change in the cycle) was 0.58 mU/l; the acrophase (the delay from midnight (0 degrees) of the highest level in the rhythm) was −9.9 degrees. In contrast, severely ill patients showed only slight and anticipated elevations of serum TSH levels (mesor 0.93 mU/l, amplitude 0.22 mU/l, acrophase +82.4 degrees). Moreover, whereas the episodic TSH secretion in healthy individuals consisted of 5–8 pulses/24 h, mainly clustered around midnight, only one pulse of reduced amplitude was detected in two of the eight severely ill patients and no pulses in the other six. Since earlier studies have indicated that the loss of TSH pulsatility is associated with the relative insensitivity of the thyrotrophs to low thyroid hormone levels and our analytical procedures have demonstrated that 24 h pulsatile pattern of TSH closely overlapped with baseline TSH secretion, it seems reasonable to assume that low-thyroid-hormone state, deficient pulsatile TSH secretion and altered nyctohemeral TSH periodicity do not coincide by chance, but that there is a causal relationship between such abnormalities in severely ill patients. Nicola Custro, Cattedra di Patologia Medica, Via del Vespro, n.141, 90127 Palermo, Italy

Thyroidal inhibition of chicken pituitary growth hormone: alterations in secretion and accumulation of newly synthesized hormone

1991 ◽  
Vol 131 (1) ◽  
pp. 39-48 ◽  
Author(s):  
R. J. Denver ◽  
S. Harvey
Keyword(s):  
Thyroid Hormone ◽  
Mammalian Species ◽  
Inhibitory Effect ◽  
Stimulatory Action ◽  
Thyrotrophin Releasing Hormone ◽  
Gh Secretion ◽  
Direct Inhibitory Effect ◽  
Hormone Exposure

ABSTRACT Hypothyroidism reduces GH synthesis and release in several mammalian species, in which thyroid hormone directly stimulates GH gene transcription. In contrast, hypothyroidism stimulates GH secretion in birds, in which thyroid hormone directly inhibits pituitary GH release. We have, therefore, investigated the effects of thyroid status on the accumulation of newly synthesized GH in the pituitaries of 8- to 10-week-old Leghorn cockerels in vitro and in vivo. The incorporation of [35S]methionine into immunoprecipitable GH ([35S] GH) was increased, over a 4-h incubation period, in glands from birds made hypothyroid by injections of methimazole (50 mg/kg day for 10 days) in comparison with glands from vehicle-injected controls. Treatment with tri-iodothyronine (T3, 100 μg/kg per day for 10 days) in vivo did not significantly alter the accumulation of [35S]GH in vitro but did block the release of [35S]GH in response to a GH secretagogue (thyrotrophin-releasing hormone; exposure to 280 nmol/l for 30 min) and reduced immunoassayable pituitary GH content. Pretreatment of glands from euthyroid birds with T3 (100 nmol/l) in vitro (for 20 h) reduced the basal accumulation of [35S]GH as well as that induced by another GH secretagogue (GH-releasing factor; 100 nmol/l) during a 6-h labelling period. These results show that, unlike the generally stimulatory action of thyroid hormone in mammals, in birds, T3 exerts a direct inhibitory effect on the accumulation of newly synthesized pituitary GH. Journal of Endocrinology (1991) 131, 39–48

scholarly journals Desethylamiodarone antagonizes the effect of thyroid hormone at the molecular level

2001 ◽  
pp. 59-64 ◽  
Author(s):  
F Bogazzi ◽  
L Bartalena ◽  
S Brogioni ◽  
A Burelli ◽  
F Raggi ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Molecular Mechanisms ◽  
Thyroid Hormone Receptor ◽  
Molecular Level ◽  
Inhibitory Effect ◽  
Mobility Shift ◽  
Down Regulation ◽  
Nih3t3 Cells ◽  
Peripheral Tissues

OBJECTIVE: To evaluate the molecular mechanisms of the inhibitory effects of amiodarone and its active metabolite, desethylamiodarone (DEA) on thyroid hormone action. MATERIALS AND METHODS: The reporter construct ME-TRE-TK-CAT or TSHbeta-TRE-TK-CAT, containing the nucleotide sequence of the thyroid hormone response element (TRE) of either malic enzyme (ME) or TSHbeta genes, thymidine kinase (TK) and chloramphenicol acetyltransferase (CAT) was transiently transfected with RSV-TRbeta into NIH3T3 cells. Gel mobility shift assay (EMSA) was performed using labelled synthetic oligonucleotides containing the ME-TRE and in vitro translated thyroid hormone receptor (TR)beta. RESULTS: Addition of 1 micromol/l T4 or T3 to the culture medium increased the basal level of ME-TRE-TK-CAT by 4.5- and 12.5-fold respectively. Amiodarone or DEA (1 micromol/l) increased CAT activity by 1.4- and 3.4-fold respectively. Combination of DEA with T4 or T3 increased CAT activity by 9.4- and 18.9-fold respectively. These data suggested that DEA, but not amiodarone, had a synergistic effect with thyroid hormone on ME-TRE, rather than the postulated inhibitory action; we supposed that this was due to overexpression of the transfected TR into the cells. When the amount of RSV-TRbeta was reduced until it was present in a limited amount, allowing competition between thyroid hormone and the drug, addition of 1 micromol/l DEA decreased the T3-dependent expression of the reporter gene by 50%. The inhibitory effect of DEA was partially due to a reduced binding of TR to ME-TRE, as assessed by EMSA. DEA activated the TR-dependent down-regulation by the negative TSH-TRE, although at low level (35% of the down-regulation produced by T3), whereas amiodarone was ineffective. Addition of 1 micromol/l DEA to T3-containing medium reduced the T3-TR-mediated down-regulation of TSH-TRE to 55%. CONCLUSIONS: Our results demonstrate that DEA, but not amiodarone, exerts a direct, although weak, effect on genes that are regulated by thyroid hormone. High concentrations of DEA antagonize the action of T3 at the molecular level, interacting with TR and reducing its binding to TREs. This effect may contribute to the hypothyroid-like effect observed in peripheral tissues of patients receiving amiodarone treatment.

Regulation of CRH-induced secretion of ACTH and corticosterone by SOM230 in rats

2005 ◽  
Vol 153 (3) ◽  
pp. R7-R10 ◽  
Author(s):  
A P Silva ◽  
P Schoeffter ◽  
G Weckbecker ◽  
C Bruns ◽  
H A Schmid
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Plasma Concentrations ◽  
Inhibitory Effect ◽  
Corticotropin Releasing Hormone ◽  
Acth Secretion ◽  
Releasing Hormone ◽  
Corticosterone Secretion ◽  
Corticosterone Release ◽  
Acth Release

Objective: Adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome is biochemically characterized by increased plasma concentrations of ACTH inducing hypersecretion of cortisol. Somatostatin is known to inhibit ACTH secretion, and in vitro data have shown the inhibition of ACTH secretion by agonists activating sst2 and sst5 receptors. The present study aimed to determine the inhibitory effect of the multireceptor ligand SOM230, compared with the sst2-preferring agonist octreotide, on corticotropin-releasing hormone (CRH)-stimulated secretion of ACTH and corticosterone in rats. Methods: Secretion of ACTH and corticosterone was induced by i.v. application of CRH (0.5 μg/kg) in rats pretreated 1 h before by i.v. application of SOM230 (1, 3, or 10 μg/kg), octreotide (10 μg/kg) or NaCl 0.9%. Results: SOM230 (3 and 10 μg/kg) inhibited CRH-induced ACTH release by 45±3% and 51±2%, respectively, and corticosterone release by 43±5% and 27±16%, respectively. 10 μg/kg of octreotide tended to be less potent at inhibiting ACTH release (34±6% inhibition) and did not alter the secretion of corticosterone. Conclusion: SOM230 has a stronger inhibitory effect on ACTH and corticosterone secretion than octreotide in rats. This difference can be explained by its higher affinity to sst1, sst3 and especially sst5 receptors compared with octreotide.

scholarly journals Synthesis and In Vitro Screening of Novel Heterocyclic β-d-Gluco- and β-d-Galactoconjugates as Butyrylcholinesterase Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2833
Author(s):  
Krešimir Baumann ◽  
Lorena Kordić ◽  
Marko Močibob ◽  
Goran Šinko ◽  
Srđanka Tomić
Keyword(s):  
Active Site ◽  
Kinetic Studies ◽  
Inhibitory Effect ◽  
In Vitro Screening ◽  
Sugar Moiety ◽  
Brain Barrier Permeability ◽  
The Central Nervous System ◽  
Key Residues ◽  
Micromolar Range

The development of selective butyrylcholinesterase (BChE) inhibitors may improve the treatment of Alzheimer’s disease by increasing lower synaptic levels of the neurotransmitter acetylcholine, which is hydrolysed by acetylcholinesterase, as well as by overexpressed BChE. An increase in the synaptic levels of acetylcholine leads to normal cholinergic neurotransmission and improved cognitive functions. A series of 14 novel heterocyclic β-d-gluco- and β-d-galactoconjugates were designed and screened for inhibitory activity against BChE. In the kinetic studies, 4 out of 14 compounds showed an inhibitory effect towards BChE, with benzimidazolium and 1-benzylbenzimidazolium substituted β-d-gluco- and β-d-galacto-derivatives in a 10–50 micromolar range. The analysis performed by molecular modelling indicated key residues of the BChE active site, which contributed to a higher affinity toward the selected compounds. Sugar moiety in the inhibitor should enable better blood–brain barrier permeability, and thus increase bioavailability in the central nervous system of these compounds.

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