THE ROLE OF MELATONIN IN THE REGULATION OF THYROTROPHIN SECRETION

1968 ◽  
Vol 57 (3) ◽  
pp. 363-373 ◽  
Author(s):  
J. N. Panda ◽  
C. W. Turner ◽  
Mary Powell

ABSTRACT The fact that melatonin, a pineal substance, causes a depression in thyroid function of prepuberal rats has been reported. A possible site of this action on the thyroid gland has been studied by estimating the TSH content of blood and hypophysis in rats from 35 days to 65 days of age. Haemagglutination-inhibition technique has been used to assay very small amounts of TSH in plasma. Rats receiving 100 μg of melatonin daily for 10 days were sacrificed at 35, 45, 55 and 65 days of age. The mean thyroid weight of each group was markedly higher than that of the corresponding controls. The plasma TSH/ml level was higher in experimental groups, with a marked decrease (0.10 > P > 0.05) in TSH/mg of hypophysis (wet), especially at 45 and 55 days of age. Rats similarly treated with 400 μg/100 g body weight of tapazole daily for 10 days and sacrificed at 45 and 55 days of age showed higher plasma and lower hypophyseal TSH levels than the controls and the results were comparable to those of the melatonin treated groups. The dry-fat-free tissue of the thyroid glands of the melatonin treated groups were higher than the corresponding controls and their DNA content was significantly higher (0.050 > P > 0.025) also, indicating hyperplasia and hypertrophy of the thyroid glands resulting from the action of melatonin. The histological picture of the melatonin treated animals showed goitrogenic effect. It may be concluded from these data that melatonin exerts its regulatory effect on TSH secretion directly acting on the thyroid gland and in some way inhibiting thyroid hormone synthesis or release.

1984 ◽  
Vol 105 (4) ◽  
pp. 567-570 ◽  
Author(s):  
Barbara Jarzab ◽  
Franciszek Kokot ◽  
Agata Bafdys

Abstract. Immunoreactive calcitonin (I-CT) was assayed in rat thyroid glands from foetuses with a gestational age of 15.5–22 days. The mean content of the hormone was 455.0 ± 35.8 ng/gland. A positive linear correlation was found between the I-CT content in the thyroid glands and the gestational age of the foetuses. I-CT was also present in rat placentae from 10.5–21.5 days old pregnancies. A mean placental concentration of 4.5 ± 1.2 ng I-CT/mg wet tissue was found. The highest hormone concentrations were observed in placentae from 10.5 day old foetuses, displaying a progressive fall during the further course of pregnancy. It is concluded that the rat foetal thyroid gland produces I-CT beginning from a gestational age of 15.5 days'. The need for further investigations into a possible role of CT in transplacental calcium transport is also indicated.


1996 ◽  
Vol 16 (3) ◽  
pp. 259-267 ◽  
Author(s):  
J H Mitchell ◽  
F Nicol ◽  
G J Beckett ◽  
J R Arthur

ABSTRACT The stimulation of thyroid hormone synthesis in iodine deficiency may increase the requirement for the selenoproteins which are involved in thyroid hormone synthesis in the thyroid gland. Selenoenzyme activity and expression were investigated in the thyroid and liver of second generation selenium-and/or iodine-deficient rats. Selenium deficiency caused substantial decreases in hepatic seleniumcontaining type I iodothyronine deiodinase (ID-I) and cytosolic glutathione peroxidase (cGSHPx) activities and mRNA abundances, but phospholipid hydroperoxide glutathione peroxidase (phGSHPx) activity was only 55% of selenium-supplemented control levels, despite the absence of change in its mRNA abundance. Selenoenzyme mRNA concentrations were maintained at control levels in thyroid glands from the selenium-deficient rat pups. Despite this, a differential effect was observed in selenoenzyme activities: ID-I activity was decreased to 61%, cGSHPx activity to 45% and phGSHPx to 29% of that in selenium-adequate controls. In iodine-deficient thyroid glands, mRNA levels were increased 2·2, 50 and 2·8 times for ID-I, cGSHPx and phGSHPx respectively. ID-I and cGSHPx enzyme activities were also increased but the activity of phGSHPx was decreased despite the high mRNA abundance. Thyroid selenoprotein mRNA levels were also increased in combined selenium and iodine deficiency but again there were differential effects on enzyme activities, with ID-I activity increased, cGSHPx unchanged and phGSHPx decreased. Thus, iodine deficiency may produce an oxidant stress on the thyroid gland, increasing the requirement for selenium to maintain selenoenzyme activity. When dietary supplies of selenium are limiting, thyroid selenoprotein mRNA levels are increased to compensate for overall lack of the micronutrient. Furthermore, there is a preferential supply of available selenium to ID-I and cGSHPx to allow maintenance of thyroid function.


1991 ◽  
Vol 124 (4) ◽  
pp. 386-390 ◽  
Author(s):  
Peter Weber ◽  
Ulrich Krause ◽  
Gabi Gaffga ◽  
Georg Brabant ◽  
Friedrich Manz ◽  
...  

Abstract. To evaluate the pathophysiological role of TSH in goitrogenesis we investigated pulsatile TSH secretion in 11 patients with a non-toxic goitre and in 11 healthy controls. Thyroid volume was 40 ± 10 ml in the goitre group and 15 ± 4 ml in the controls as measured by ultrasound. Blood was sampled continously via an indwelling venous catheter at 10-min intervals over 24 h. Neither the mean 24-h serum TSH levels (goitre 1.1 ± 0.5 vs controls 0.9 ± 0.4 mU/l) nor the nocturnal surge of TSH were significantly different between the two groups. The average of the TSH pulse frequency (goitre 10.8 ± 3.7 vs controls 9.6 ± 3.5 pulses/24-h) and of the TSH pulse amplitude (goitre 0.4 ± 0.2 vs controls 0.3 ± 0.1 mU TSH/l as analysed by DESADE programme (detection of secretory activity by discrete deconvolution) did not differ in the two groups. Furthermore, there was no correlation between the volume of the thyroid gland and the dynamics of the TSH secretion. We conclude that our data do not suggest a relevant pathophysiological role of TSH secretion in the development of non-toxic goitre in man.


1984 ◽  
Vol 106 (3) ◽  
pp. 338-345 ◽  
Author(s):  
G. Schaison ◽  
P. Thomopoulos ◽  
D. Leguillouzic ◽  
G. Thomas ◽  
M. Moatti

Abstract. To investigate the respective role of triiodothyronine (T3) and thyroxine (T4) in the regulation of TSH secretion, we studied the action of sodium ipodate and propylthiouracil (PTU) in 11 athyreotic patients. The lT4 replacement dose was adjusted to obtain, in each patient, a normal basal TSH level and a normal TSH response to TRH. In the 5 ipodate-treated patients (single 6 g oral dose), the mean serum T3 level fell by 64% below the baseline value and serum rT3 rose 180% above the baseline. The free T4 index (FT4I) did not change whereas the mean serum TSH concentration increased 280% above baseline values. In the 6 PTU-treated patients (250 mg orally every 6 h for 10 days), serum T3 levels fell 33%, serum rT3 increased up to 82% and the FT4I did not change. The mean serum TSH concentration increased 68% above the baseline value. Thus, the mean percentage increase in serum TSH was less in PTU- than in ipodate-treated patients (68% vs 280%). Statistical analysis of the correlation between the serum T3 decrease (ΔT3) and the serum TSH (ΔTSH) increase demonstrated that for the same T3 diminution, the ipodate-treated group displayed higher increase of TSH than the PTU-treated patients. In the rat, PTU interferes with the 5'-deiodination of T4 in the liver and kidney but not in the pituitary, while ipodate appears to have the same effect in all tissues. If this holds true for human subjects, our data strongly suggest that circulating T4 (through its intrapituitary conversion to T3) shares with serum T3 the capacity to regulate TSH secretion in man.


2018 ◽  
Vol 19 (9) ◽  
pp. 2792 ◽  
Author(s):  
Marta Ząbczyńska ◽  
Kamila Kozłowska ◽  
Ewa Pocheć

The key proteins responsible for hormone synthesis in the thyroid are glycosylated. Oligosaccharides strongly affect the function of glycosylated proteins. Both thyroid-stimulating hormone (TSH) secreted by the pituitary gland and TSH receptors on the surface of thyrocytes contain N-glycans, which are crucial to their proper activity. Thyroglobulin (Tg), the protein backbone for synthesis of thyroid hormones, is a heavily N-glycosylated protein, containing 20 putative N-glycosylated sites. N-oligosaccharides play a role in Tg transport into the follicular lumen, where thyroid hormones are produced, and into thyrocytes, where hyposialylated Tg is degraded. N-glycans of the cell membrane transporters sodium/iodide symporter and pendrin are necessary for iodide transport. Some changes in glycosylation result in abnormal activity of the thyroid and alteration of the metabolic clearance rate of hormones. Alteration of glycan structures is a pathological process related to the progression of chronic diseases such as thyroid cancers and autoimmunity. Thyroid carcinogenesis is accompanied by changes in sialylation and fucosylation, β1,6-branching of glycans, the content and structure of poly-LacNAc chains, as well as O-GlcNAcylation, while in thyroid autoimmunity the main processes affected are sialylation and fucosylation. The glycobiology of the thyroid gland is an intensively studied field of research, providing new data helpful in understanding the role of the sugar component in thyroid protein biology and disorders.


2006 ◽  
Vol 190 (1) ◽  
pp. 157-170 ◽  
Author(s):  
Robert Opitz ◽  
Achim Trubiroha ◽  
Claudia Lorenz ◽  
Ilka Lutz ◽  
Sabine Hartmann ◽  
...  

The uptake of iodide represents the first step in thyroid hormone synthesis by thyroid follicular cells and is mediated by the sodium-iodide symporter (NIS). In mammals, expression of NIS is stimulated by TSH and transcription of the NIS gene involves regulation by the thyroid-specific transcription factors Pax8 and Nkx2.1. In this study, we examined the mRNA expression of NIS, Pax8 and Nkx2.1 in the thyroid gland of Xenopus laevis tadpoles by semi-quantitative reverse transcriptase (RT)-PCR. During spontaneous metamorphosis, NIS mRNA expression was low in premetamorphic tadpoles, increased throughout prometamorphosis, and peaked at climax stage 60. Analysis of TSH β-subunit (TSHβ) mRNA in the pituitary of the same tadpoles revealed a close temporal relationship in the expression of the two genes during metamorphosis, suggesting a regulatory role of TSH in the developmental expression of NIS. Treatment of tadpoles with goitrogenic compounds (sodium perchlorate and ethylenethiourea) increased TSHβ mRNA expression (approximately twofold) and caused thyroid gland hyperplasia, confirming that feedback along the pituitary–thyroid axis was operative. Analysis of gene expression in the thyroid gland revealed that goitrogen treatment was correlated with increased expression of NIS mRNA (~20-fold). In the thyroid gland organ culture experiments, bovine TSH (bTSH; 1 mU/ml) strongly induced NIS mRNA expression. This effect was mimicked by co-culture of thyroid glands with pituitaries from stage 58 tadpoles and by agents that increase intracellular cAMP (forskolin, dibutyryl-cAMP). In addition, it could be shown that thyroid glands of X. laevis tadpoles express Pax8 and Nkx2.1 mRNA in a developmentally regulated manner and that ex vivo treatment of thyroid glands with bTSH, forskolin, and cAMP analogs increased the expression of Pax8 and Nkx2.1 mRNA. This is the first report on developmental profiles and hormonal regulation of thyroid gland gene expression in amphibian tadpoles and, together, results reveal a critical role of TSH in the regulation of NIS mRNA expression in the thyroid gland of X. laevis tadpoles.


1963 ◽  
Vol 26 (2) ◽  
pp. 219-231 ◽  
Author(s):  
P. J. O'CONNOR ◽  
L. G. SKINNER

SUMMARY The haemagglutination—inhibition technique has been examined as a method of estimating human growth hormone (HGH) and the need for rigid standardization of the procedures involved is stressed. Examination of antisera to a Raben type preparation by immunodiffusion and haemagglutination—inhibition procedures showed the presence of antibodies to albumin and γ-globulin as well as to HGH. The presence of these contaminating antibodies did not appear to interfere with the endpoints obtained in the haemagglutination—inhibition reactions. Within its limitations the technique has been found suitable for the assay of solutions of purified HGH. The mean level of HGH in six normal adult human sera was estimated as 261 ± 23·6 μg./l. (± s.e.) which is similar to the values obtained by other workers, but the validity of this mean value is questioned.


1960 ◽  
Vol 199 (2) ◽  
pp. 203-208 ◽  
Author(s):  
Emanuel Silverstein ◽  
Leon Sokoloff ◽  
Olaf Mickelsen ◽  
George E. Jay

Strain differences were observed in the T/S ratios and thyroid weights of 505 mice comprising six inbred strains and three pairs of F1 hybrids. These differences were not accounted for by variations in body weight or degree of blocking of iodine incorporation into organic compounds by Tapazole. There was an apparently inverse relationship between the mean T/S ratios of the various strains and the relative weights of the thyroid glands. The weights of the thyroid glands increased progressively from 7 to 16 months of age in each strain even though there were only small changes in body weight. The T/S ratios were relatively unchanged between these ages. The weight of the thyroid gland appeared to be influenced by the interaction between the strain of animal, diet fed and possibly by obesity. The mean plasma PBI values ranged from 0.9 to 3.5 µg/ml and showed no relationship to the T/S ratios.


1974 ◽  
Vol 75 (4) ◽  
pp. 699-706 ◽  
Author(s):  
T. Hjort ◽  
Th. Friis ◽  
U. Birk Lauridsen ◽  
I. Persson

ABSTRACT Thyroglobulin in serum was demonstrated by a haemagglutination-inhibition technique and a reversed haemagglutination technique. Circulating thyroglobulin was found in 12 of 15 hyperthyroid patients – both before and during treatment with methylthiouracil – but in none of 12 euthyroid subjects. In three hyperthyroid patients it was not possible to determine thyroglobulin, as thyroglobulin antibody was present in the serum. After TSH stimulation thyroglobulin appeared in the serum of nine of the 12 euthyroid subjects and the thyroglobulin level increased in five of the 12 untreated and six of the 12 treated hyperthyroid patients. The serum thyroxine, T3 uptake in resin and 131I uptake in the thyroid gland at 4 and 24 h were increased after TSH stimulation in all the euthyroid cases; the hyperthyroid patients (both before and during treatment), however, only showed a slight but significant increase in serum thyroxine and 4 h 131I uptake, while the T3 uptake in resin and the 24 h 131I uptake did not rise at all. LATS was found in serum of only five of 15 untreated hyperthyroid patients. No significant changes in the LATS content could be detected during treatment. The increased content of thyroglobulin in the serum of hyperthyroid patients seems to be due neither to greater sensitivity to TSH nor to the influence of LATS.


1975 ◽  
Vol 79 (4) ◽  
pp. 729-739 ◽  
Author(s):  
M. Yusoff Dawood

ABSTRACT Both serum progesterone and serum unconjugated oestradiol-17β (Oe2) were measured by competitive protein binding assay and radioimmunoassay respectively in 42 cases of unaborted hydatidiform mole. Serum human chorionic gonadotrophin (HCG) was measured by a haemagglutination-inhibition technique. In 26 cases of intact molar pregnancies without theca lutein cysts (TLC), serum progesterone ranged from 18.0 to 289.0 ng/ml with a mean ± standard error of the mean (sem) of 65.9 ± 13.1 ng/ml; serum Oe2 ranged from 4.0 to 37.0 ng/ml with a mean ± sem of 17.9 ± 1.9 ng/ml; serum HCG ranged from 60 to 1920 IU/ml with a mean ± sem of 531.5 ± 105.7 IU/ml. In contrast, 16 cases of intact molar pregnancies with TLC had serum progesterone ranging from 34.1 to 288.0 ng/ml with a mean ± sem of 134.1 ± 2.4 ng/ml; serum Oe2 ranging from 1.7 to 76.3 ng/ml with a mean ± sem of 31.5 ± 5.3 ng/ml; serum HCG ranging from 320 to 2560 IU/ml with a mean ± sem 1400 ± 196.2 ng/ml. The differences between the mean of these three hormones in hydatidiform mole with and without TLC were significant (progesterone: P < 0.005; Oe2: P < 0.0125; HCG: P < 0.005). There was a significant correlation between serum HCG and serum Oe2 (coefficient of correlation r =+0.3565, P < 0.0125) and between serum Oe2 and serum progesterone (r = +0.3787, P < 0.0125). There was no significant difference in the mean levels of serum progesterone, Oe2 and HCG in hydatidiform mole with and without subsequent malignant sequelae. The mean ratios of Oe2/progesterone were essentially similar in moles with and without TLC and with and without malignant sequelae. The significance of these findings are discussed.


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