Thyroid activity in response to some gonadal steroids in methallibure-treatedHeteropneustes fossilis (Bloch)

Summary Methallibure treatment is as effective as hypophysectomy in reducing thyroid activity inH. fossilis. Sex steroids (TP and EB) administration restored thyroid activity in methallibure-treated females to normal level, but failed to elicit any response in males. This drug seems to block TSH secretion and thyroid hormone synthesis inH. fossilis.Financial assistance in the form of SRF from ICAR, New Delhi to one of us (R.B.R.), gift of methallibure from ICI Ltd., UK and TSH from NIH, USA, to T.P.S. are gratefully acknowledged.     

Chromatosomes are not produced from Tetrahymena chromatin by micrococcal nuclease digestion

The subnucleosomal organization of Tetrahymena chromatin, which has an unusual H1 histone, was investigated by NaCl extraction and micrococcal nuclease digestion of nuclei. It was found that Tetrahymena histone H1 is extracted with 0.35 M NaCl, whereas bovine thyroid H1 is not. Micrococcal nuclease digestion of Tetrahymena nuclei did not yield chromatosomes as a stable intermediate, whereas digestion of bovine thyroid nuclei did.     

Catfish blood chemistry under environmental stress

Blood chemistry of Heteropneustes fossilis exposed to sewage, fertilizers and insecticides showed signs of anemia, dehydration and disturbance in the pituitary-interrenal endocrine axis and the excretory function of gills. Hepatic and renal tissue damage was also indicated.     

Chromatosomes are not produced fromTetrahymena chromatin by micrococcal nuclease digestion

Summary The subnucleosomal organization ofTetrahymena chromatin, which has an unusual H1 histone, was investigated by NaCl extraction and micrococcal nuclease digestion of nuclei. It was found thatTetrahymena histone H1 is extracted with 0.35 M NaCl, whereas bovine thyroid H1 is not. Micrococcal nuclease digestion ofTetrahymena nuclei did not yield chromatosomes as a stable intermediate, whereas digestion of bovine thyroid nuclei did.     

Estimation of plasma thyroxine concentration in ducks in relation to different environmental and experimental conditions.

Plasma thyroxine concentration was measured in ducks by the thyroxine-binding globulin technique. The assay allowed us to detect annual variations in thyroid activity as well as significant changes after starvation or cold exposure. No detectable thyroxine was formed in surgically thyroidectomized ducks.     

Occurrence of carotid labyrinth in the catfish group of teleost fishes

Summary A structure similar in topography and morphology to the carotid labyrinth of amphibians has been found in 4 catfishes, namely,Clarias batrachus, Heteropneustes fossilis, Rita rita andMystus seenghala. The present finding of the presence of the carotid labyrinth in fishes is the first report, and the results are discussed in the light of the amphibious habit of these catfishes.We are grateful to Prof. U.S. Srivastava for providing laboratory facilities and for encouragement. The work was financially supported by the S.C.S.T., U.P. which is thankfully acknowledged.     

A histochemical demonstration of the Na+ + K+-ATPase activity in the thyroid and the effect of cyclic adenosine monophosphate (c-AMP).

With a suitable modification of the Farquhar and Palade technique the Na+ + K+-ATPase activity in guinea-pig thyroid is demonstrated. The addition of c-AMP (5 X 10(-6) M or 1.5 X 10(-5) M) to the incubation media produced an apparent intensification of the Na+ + K+ -ATPase activity in the thyroid.     

Estimation of plasma thyroxine concentration in ducks in relation to different environmental and experimental conditions

Summary Plasma thyroxine concentration was measured in ducks by the thyroxine-binding globulin technique. The assay allowed us to detect annual variations in thyroid activity as well as significant changes after starvation or cold exposure. No detectable thyroxine was formed in surgically thyroidectomized ducks.Supproted by CNRS and the Department of Biology of the CEA.     

A new neurosecretory system in fish,located in the gill region

Summary A peculiar neurosecretory system is reported in 6 teleost species;Clarias batrachus, Heteropneustes fossilis, Mystus seenghala, Ompak pabda, Glassogobius giuris andNotopterus notopterus. It is located in the gill region close to the pseudobranch or to the carotid labyrinth. The neurosecretory cells have been identified using stains specific for neurosecretion. The results are discussed in the light of the association of the neurosecretory system with the pseudobranch or the carotid labyrinth, and the airbreathing habit of these fishes.We are grateful to Prof. U.S. Srivastava for providing laboratory facilities and for encouragement. The work was financially supported by U.G.C. Research Project grant awarded to C.B.L.S., which is thankfully acknowledged. Thanks are due to M. Seal and Amarlata for technical help rendered.     

Molecular and structural effects of inverse agonistic mutations on signaling of the thyrotropin receptor – a basally active GPCR

Several mutations that decrease the basal signaling activity of G-protein coupled receptors (GPCRs) with pathogenic implications are known. Here we study the molecular mechanisms responsible for this phenotype and investigate how basal and further activated receptor conformations are interrelated. In the basally active thyroid stimulating hormone receptor (TSHR) we combined spatially-distant mutations with opposing effects on basal activity in double-mutations and characterized mutant basal and TSH induced signaling. Mutations lowering basal activity always have a suppressive influence on TSH induced signaling and on constitutively activating mutations (CAMs). Our results suggest that the conformation of a basally ‘silenced’ GPCR might impair its intrinsic capacity for signaling compared to the wild-type. Striking differences in conformation and intramolecular interactions between TSHR models built using the crystal structures of inactive rhodopsin and partially active opsin help illuminate the molecular details underlying mutations decreasing basal activity. G. Kleinau, H. Jaeschke: These two authors contributed equally to this work. Received 31 July 2008; received after revision 12 September 2008; accepted 19 September 2008     

Ontogenesis of monoamine oxidase in the thyroid gland of rats

Summary During postnatal development, MAO activity in the thyroid gland of male rats increases until day 16, when adult values are reached.     

Development of thyroid peroxidase activity during the early stage of iodine deficiency in the hypophysectomized rat]

The iodide-peroxidase activity of the thyroid gland remains, in hypophysectomized Rats maintained on a low iodine diet, below normal value. This result suggests that the early increase of peroxidase activity observed in control Rats maintained on a low iodine diet is TSH dependent.     

A histochemical demonstration of the Na++K+-ATPase activity in the thyroid and the effect of cyclic adenosine monophosphate (c-AMP)

Summary With a suitable modification of the Farquhar and Palade technique the Na⁺+K⁺-ATPase activity in guineapig thyroid is demonstrated. The addition of c-AMP (5×10^–6 M or 1.5×10^–5 M) to the incubation media produced an apparent intensification of the Na⁺+K⁺-ATPase activity in the thyroid.This work was supported by a grant from ZMNU of Serbia.     

Inactivation of Ret/Ptc1 oncoprotein and inhibition of papillary thyroid carcinoma cell proliferation by indolinone RPI-1

Genetic alterations causing oncogenic activation of the RET gene are recognized as pathogenic events in papillary and medullary thyroid carcinomas. Inhibition of Ret oncoprotein functions could thereby represent a specific therapeutic approach. We previously described the inhibitory activity of the 2-indolinone derivative RPI-1 (formerly Cpd1) on the tyrosine kinase activity and transforming ability of the products of the RET/PTC1 oncogene exogenously expressed in murine cells. In the present study, we investigated the effects of RPI-1 in the human papillary thyroid carcinoma cell line TPC-1 spontaneously harboring the RET/PTC1 rearrangement. Treatment with RPI-1 inhibited cell proliferation and induced accumulation of cells at the G2 cell cycle phase. In treated cells, Ret/Ptc1 tyrosine phosphorylation was abolished along with its binding to Shc and phospholipase C, thereby indicating abrogation of constitutive signaling mediated by the oncoprotein. Activation of JNK2 and AKT was abolished, thus supporting the drug inhibitory efficacy on downstream pathways. In addition, cell growth inhibition was associated with a reduction in telomerase activity by nearly 85%. These findings in a cellular context relevant to the pathological function of RET oncogenes support the role of Ret oncoproteins as useful targets for therapeutic intervention, and suggest RPI-1 as a promising candidate for preclinical development in the treatment of thyroid tumors expressing RET oncogenes.Received 31 December 2002; received after revision 21 February 2003; accepted 10 April 2003     

Effect of adrenalectomy and dexamethasone treatment on the monoamine oxidase activity in the thyroid gland of the rat

Summary Adrenalectomy increased MAO activity in the thyroid gland of rats. The administration (200 g/100 g daily for 7 days) to adrenalectomized rats decreased MAO activity below levels of intact controls.     

Effects of altered thyroid state on the inhibition produced by locus coeruleus in purkinje cells in the rat

Summary The number of cerebellar Purkinje cells inhibited after locus coeruleus stimulation was found to be greater in hyperthyroid rats than in control healthy animals; these in turn showed a higher percentage of inhibited cells than hypothyroid rats. It is concluded that thyroid hormone is capable of modulating synaptic activity in the LC-PC pathway.     

Studies on the thyroid in transgenic mice expressing the genes for human and bovine growth hormone

The thyroid glands of transgenic mice (TM) expressing the genes for human (h) and bovine (b) growth hormone (GH) were studied. The percentages of larger follicles in hGH TM of either sex were significantly greater than in the corresponding normal littermates, and follicles ranging up to 350 microns in diameter were present in male hGH TM. In contrast, thyroid follicles were only slightly enlarged in male bGH TM, and were unchanged in female bGH TM. The serum concentrations of T4 were significantly decreased in male bGH TM and not altered in the other groups. Serum concentrations of T3 were slightly, but significantly increased in female hGH TM and female bGH TM, but were unaffected in male TM of either type. Since the principal difference between these foreign GHs in rodents is the additional lactogenic activity of human GH, these results may indicate that the effects of prolactin can influence the development of the thyroid.     

Effects of hypo- and hyperthyroidism on the activity of cystathionase in mammalian parenchymatous organs during early development

Summary In rats after neonatal thyroid destruction, cystathionase in liver and pancreas increased, but the enzyme activity in kidneys decreased. Substitution with thyroxine corrected these changes. Excess of thyroxine, too, had an effect on tissue cystathionase.     

Annual cycle of plasma testosterone and thyroxine in the European badger (Meles meles L.)]

In the male European Badger there are important variations in the plasma testosterone and thyroxine levels during the annual cycle. During the summer, plasma testosterone concentrations are low while plasma thyroxine rises to a very high level. In winter, when the thyroid activity is minimal, testicular activity increases. From February to May, the plasma testosterone remains at a high level, and then, after a sudden fall, a second peak occurs in June at which time the concentration of thyroxine is low.     

Splenic B-cell activation in lipopolysaccharide-non-responsive C3H/HeJ mice by lipopolysaccharide ofPorphyromonas gingivalis

Porphyromonas gingivalis 381 lipopolysaccharide (LPS) definitely exhibited mitogenic activity in purified B-cells, separated from spleens of LPS-responsive C3H/HeN mice and LPS-non-responsive C3H/HeJ mice by using a magnetic cell sorting system. The mitogenic activity induced byP. gingivalis LPS was incompletely inhibited by polymyxin B.P. gingivalis LPS also induced a higher production of interleukin-6 (IL-6) in splenic B-cells of C3H/HeN mice as compared withEscherichia coli LPS. Furthermore,P. gingivalis LPS, but notE. coli LPS, induced definite IL-6 production in C3H/HeJ mice.P. gingivalis LPS increased tyrosine, serine/threonine phosphorylation of proteins with various major induced bands in splenic B-cells of both C3H/HeN and C3H/HeJ mice. Additionally, radioiodinatedP. gingivalis LPS, similarly toE. coli LPS, bound to a 73-kDa protein on C3H/HeJ as well as C3H/HeN B-cells. ThusP. gingivalis LPS may activate B-cells of C3H/HeJ as well as C3H/HeN mice via the LPS-specific binding protein on the cells.