Biomedical subjects

T Iriuchijima

Publications and source records attributed to T Iriuchijima.

At least 37 records · Page 2Linked to original sources

PubMed1993

Alteration by prolonged oral administration of a thyrotropin-releasing hormone analog, TA-0910, of the pituitary-thyroid axis in subjects with brain stroke.

We evaluated whether prolonged oral administration of a novel analog of thyrotropin-releasing hormone (TRH), TA-0910, may change the pituitary-thyroid axis in human subjects with brain stroke. The subjects were given one oral dose of 2.5-20 mg of TA-0910 daily for 8 weeks, and then blood levels of TA-0910, thyroid hormones and thyrotropin (TSH) were measured. Plasma levels of TA-0910 were elevated with increasing doses. After administration of TA-0910, the basal levels of thyroid hormones and TSH had a tendency to increase and decrease, respectively, but those changes remained in the normal range. The secretion of TSH in response to TRH was not significantly affected by TA-0910 administration. No significant changes in other pituitary hormones were observed after TA-0910 administration. The present data indicate that prolonged oral administration of TA-0910 did not significantly alter the pituitary-thyroid axis in subjects with brain stroke.

Administration, Oral↗

PubMed1992

Characterization of human thyrotropin receptor-related peptide-like immunoreactivity in peripheral blood of Graves' disease.

An antiserum raised against an alignment of amino acid-(32-56), termed TSHRP-1, in the extracellular domain of human thyrotropin (TSH) receptor was used to identify the TSH receptor-like substance in plasma of Graves' disease. The dilution curve of plasma TSHRP-1-like immunoreactivity was observed in a manner parallel to the standard synthetic peptide curve in radioimmunoassay, and its molecular weight estimated approximately 60 kDa. The amounts of TSHRP-1-like immunoreactivity were significantly higher in Graves' plasma than those in plasma of normal and hypothyroid patients due to Hashimoto's thyroiditis. The present results indicate that human peripheral blood possesses a soluble form of the extracellular domain of TSH receptor which may contribute to the pathophysiology of Graves' disease.

Biomarkers↗

PubMed1992

Differential regulation of thyrotropin-releasing hormone receptor mRNA levels by thyroid hormone in vivo and in vitro (GH3 cells).

We studied the effect of thyroid status on thyrotropin-releasing hormone receptor (TRH-R) mRNA levels both in vivo and in vitro (GH3 cells) using a cloned rat TRH-R cDNA by RT-PCR. Experimental hypothyroid rats were produced by total thyroidectomy and were then killed 7 days after the operation. TRH receptor binding in the anterior pituitary and serum TSH level were elevated approximately 2-fold and 8-fold, respectively, in 7 day thyroidectomized rats. TRH-R mRNA levels in hypothyroid rats were also increased significantly compared with those of normal rats. In GH3 cells, however, no significant change of TRH-R mRNA level was observed between cultures treated with triiodothyronine (T3, 10(-9) and 10(-7) M) and the untreated group. The present data indicate that 1) the in vivo effects of thyroid status on TRH-R mRNA levels differ from the in vitro one, and that 2) the down regulation of TRH-R binding by thyroid hormone in GH3 cells may be mediated by translational or post-translational mechanisms.

Amino Acid Sequence↗

PubMed1992

Okadaic acid inhibits the release of TSH in response to TRH and K+ from rat anterior pituitaries.

The effects of okadaic acid, a non-phorbol-12-tetradecanoate-13-acetate (non-TPA)-type tumor promoter and a potent inhibitor of protein phosphatases, on thyroid-stimulating hormone (TSH) secretion from the rat anterior pituitary were examined. Preincubation of anterior pituitaries with okadaic acid caused a time- and concentration-related decrease in a subsequent thyrotropin-releasing hormone (TRH)-stimulated TSH secretion, whereas it did not cause any changes in basal secretion of TSH. In addition, okadaic acid inhibited a subsequent high K(+)-induced TSH secretion. In contrast, ionomycin-induced TSH secretion was not inhibited by pretreatment with okadaic acid. The present results suggest that okadaic acid may block the release of TSH by inhibition of Ca2+ influx through voltage-sensitive and/or receptor-operated Ca2+ channels.

Animals↗

PubMed1992

Thyroid hormone affects the hydrolysis of inositol phospholipids in the rat hypothalamus.

We have attempted to elucidate the effect of thyroid hormone on phospholipase C-linked inositol phospholipid hydrolysis in the rat hypothalamus. Hypothalamic slices of each animal, euthyroid control, hypothyroid, and thyroxine (T4)-supplemented hypothyroid rats were labeled with [3H]myoinositol in the presence of 5 mM LiCl, and then incubated for 60 min in KHG buffer containing either vehicle or 1 mM ouabain, a Na-K ATPase inhibitor. Hypothyroidism caused a significant increase in both basal and ouabain-stimulated accumulation of [3H]inositol phosphate ([3H]IP) in hypothalamic slices, whereas supplement with T4 to hypothyroid rats resulted in a complete restoration of hypothalamic [3H]IP formation to the value of euthyroid control. The present results indicate that thyroid hormone affects phospholipase C-linked inositol phospholipid hydrolysis in the hypothalamus, suggesting that negative feedback action of thyroid hormone may occur at a post-receptor site in the hypothalamus.

Animals↗

PubMed1992

Inhibitory effects of okadaic acid on thyrotropin and prolactin secretion from rat anterior pituitaries.

The present study was undertaken to elucidate the effects of okadaic acid, a potent inhibitor of protein phosphatases, on thyrotropin (TSH) and prolactin (PRL) secretion, and on the hydrolysis of inositol phospholipids in rat anterior pituitaries. Preincubation of anterior pituitaries with okadaic acid caused a dose dependent decrease in TRH- and K(+)-induced TSH secretion, whereas basal secretion of TSH was not affected by pretreatment with okadaic acid. In contrast, okadaic acid resulted in a marked inhibition in both basal, and TRH- and K(+)-stimulated PRL release from anterior pituitaries. In addition, pretreatment with okadaic acid caused a slight, but significant decrease in the formation of [3H]inositol phosphate ([3H]IP) in rat anterior pituitaries. The present study suggests that okadaic acid blocks the release of TSH and PRL by inhibiting Ca2+ influx and that inhibitory effects of okadaic acid on PRL release are, at least in part, due to the inhibition of inositol phospholipid hydrolysis.

Animals↗

PubMed1992

Thyroid hormones regulate the formation of inositol phosphate in response to thyrotropin-releasing hormone in rat anterior pituitaries.

The effects of thyroid hormones on TSH secretion and inositol phospholipid hydrolysis in response to thyrotropin-releasing hormone (TRH) in rat anterior pituitaries were examined. Experimental hypothyroidism caused a significant increase in [3H]inositol phosphate ([3H]IP) formation in response to TRH in rat anterior pituitaries with a concomitant elevation of blood TSH. In contrast, administration of thyroxine (T4) to hypothyroid rats resulted in a complete restoration of blood TSH and TRH-stimulated [3H]IP formation to the euthyroid control value. Furthermore, in vitro pre-treatment of anterior pituitaries with triiodothyronine (T3) produced a dose-dependent decrease in both TSH secretion and the formation of [3H]IP in response to TRH. These results indicate that thyroid hormones regulate TRH receptor-linked inositol phospholipid hydrolysis in the rat anterior pituitary, suggesting that negative feedback action of thyroid hormone occurs at post receptor event in the rat anterior pituitary, which may, to a certain extent, be responsible for the underlying mechanism of T3 inhibition of TSH secretion.

Animals↗

PubMed1992

Influences of hypothyroidism on TRH concentrations and preproTRH mRNA levels in rat hypothalamus: a simple and reliable method to detect preproTRH mRNA level.

To gain further insight into the regulation of hypothalamic TRH by thyroid hormones, we measured TRH concentration in specific hypothalamic nuclei and preproTRH mRNA levels in the anterior hypothalamus. Adult male rats were decapitated 1, 7, 14 days after thyroidectomy. Micropunches by the method of Palkovitz from seven hypothalamic nuclei and median eminence were used for measurement of TRH by radioimmunoassay. As compared with normal levels, TRH concentration significantly decreased in the median eminence and five hypothalamic nuclei including paraventricular nucleus (PVN), posterior nucleus, anterior nucleus, arcuate nucleus, and ventromedial nucleus pars lateralis, by 7 days after thyroidectomy. No significant changes were observed in dorsomedial nucleus or ventromedial nucleus pars medialis until 14 days after thyroidectomy. A rapid and simple method to detect specific mRNA for preproTRH was developed using the polymerase chain reaction and a single anterior hypothalamic section. PreproTRH mRNA levels in the anterior hypothalamus increased approximately twice 7 days after thyroidectomy. These data indicate that thyroidectomy caused a marked increase in preproTRH mRNA levels of the anterior hypothalamus, while it significantly reduced TRH concentrations not only in PVN and median eminence but also in other specific hypothalamic nuclei, suggesting that these nuclei might be involved in the thyrotropin regulation in the hypothalamus.

Animals↗

PubMed1992

Identification of inositol 1,4,5-trisphosphate binding in human pheochromocytoma.

An attempt was made to identify a specific binding of inositol 1,4,5-trisphosphate (IP3) to human chromaffin cell tumors. Crude microsomal fractions of pheochromocytomas possessed significant binding sites for [3H]IP3 with high- and low-affinity constants (Kd = 5.46 and 538 nM, respectively). The binding to these sites was rapid, saturable (reached equilibrium by 1 min at 0 degrees C) and reversible. Competition studies with other inositol phosphate analogs indicated the stereotypic specific binding for IP3. Although no significant difference was observed in the binding densities of IP3 between pheochromocytomas and adrenal nonfunctioning adenomas, the values of high-affinity constants were significantly lower in the former than the latter group (5.77 +/- 1.07, n = 5 vs. 11.30 +/- 1.98 nM, n = 4, p less than 0.05). The present data indicate that characteristics of IP3 binding sites are congruous with their receptor functions and that changes in its binding sites may contribute to the biochemical dissimilitudes in pheochromocytomas.

Adenoma↗

PubMed1992

Different posttranslational processing of human preprothyrotropin-releasing hormone in the human placenta and hypothalamus.

We scrutinized the possible existence of human prepro-THR messenger RNA (mRNA) and of its posttranslational processing products in the human placenta. Human placental mRNA of preproTRH was found to have a single species identical to that predicted from the hypothalamic mRNA, and could be reverse transcribed to complementary DNA (cDNA) encoding preproTRH in a size similar to the hypothalamic counterpart by means of reverse-transcriptase-polymerase chain reaction. Five different intervening peptides, designated human TRH-associated peptide (hTAP) [hTAP-1, preproTRH(90-111); hTAP-2, preproTRH(120-132); hTAP-3, preproTRH(141-149); hTAP-4, preproTRH(158-183); hTAP-5, preproTRH(192-224)], and a TRH precursor comprising the TRH progenitor sequence (octa-TRH) were synthesized, and six different antisera raised against individual peptides were used to develop specific RIA systems. Significant concentrations of hTAP-5 and octa-TRH-like immunoreactivities were quantitated in acid extracts of human placentae. In human hypothalamic extracts, immunoreactivities of hTAP-3, hTAP-4, hTAP-5, and octa-TRH, were apparently detected. Chromotographic analysis showed a single peak corresponding to each authentic peptide in RIA systems of hTAPs detected. In placentae, a single peak of octa-TRH-like substance was observed, and two octa-TRH-like substances with different molecular weights detected in hypothalami. The present data indicate that unique posttranslational processing steps of human preproTRH differ in human placentae and hypothalami, and that the human tissues involve profound amounts of several preproTRH-related peptides which do not comprise the TRH progenitor sequence.

Aged↗

PubMed1992

[Chronic lymphocytic leukemia diagnosed after corticosteroid therapy for Evans syndrome].

A 59-year-old woman was admitted in February 1991, because of abdominal distension. On admission, she had splenomegaly, autoimmune hemolytic anemia, and idiopathic thrombocytopenic purpura. Evans syndrome had been diagnosed and daily prednisolone therapy had been performed. After this therapy, a rapid increase of lymphocytes was observed accompanied with contraction of spleen. The monoclonal proliferation of B-lymphocytes and rearrangement of JH and J kappa gene were detected and chronic lymphocytic leukemia was diagnosed. With reduction of prednisolone, the lymphocyte counts decreased and the size of the spleen returned to the previous state. It is suspected that the cause of rapid lymphocytosis in this case was due to the redistribution of lymphocytes from the spleen to the peripheral blood.

Anemia, Hemolytic↗

PubMed1991

TRH-Gly, a precursor of TRH, alters GH secretion in acromegaly.

We explored effects of a precursor of thyrotropin (TSH)-releasing hormone (TRH), TRH-Gly, on growth hormone (GH) secretion in acromegaly. Intravenous injection of TRH-Gly produced a profound increase in GH secretion in eight, decrease in two, and no response in five out of a total fifteen patients. The magnitude of GH responsiveness to TRH-Gly was significantly correlated with that induced by TRH (r = 0.824, P less than 0.01). In contrast, TRH-Gly did not induce secretion of TSH or prolactin. The present data suggest that TRH-Gly may participate in regulating GH secretion in some patients with acromegaly and that TRH-Gly-induced GH secretion may be due at least in part to TRH-associated mechanisms underlying GH secretion.

Acromegaly↗

PubMed1991

Recognition by anti-idiotypic anti-thyrotropin-releasing hormone (TRH) antibody of rat TRH receptors.

We asked whether anti-idiotypic antibodies raised against anti-TRH antibody could bind to TRH receptors in the rat anterior pituitary and brain. Six rabbits were immunized with IgG from a rabbit anti-TRH antiserum. One anti-idiotypic antibody caused strong, dose-dependent inhibition in anti-TRH antibody-binding to [125]I-TRH. This inhibition was not observed after treatment with goat anti-rabbit IgG antibody. The anti-idiotypic anti-TRH antibody significantly immunoprecipitated digitonin-solubilized pituitary TRH receptors. When eluates of digitonin-solubilized membranes which were adsorbed by either an anti-idiotypic anti-TRH IgG-, normal rabbit IgG-linked affinity column or control column were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and visualized by silver stain, only the former eluate showed two bands under nonreducing conditions; one corresponded to a molecular weight marker of 200K, the other to 100K. Western blotting analysis with an anti-idiotypic anti-TRH antiserum showed a single band of molecular weight 56K under reducing conditions. The present study indicates that one can make anti-idiotypic antibodies that specifically recognize TRH receptors.

Animals↗

PubMed1991

Central hypothyroidism due to isolated TRH deficiency in a depressive man.

A depressive man was evaluated for developing chronic fatigue and cold intolerance, in whom laboratory findings showed decreased thyroid hormone levels (T4, 2.7 micrograms dl-1; T3, 0.76 ng ml-1) with normal blood levels of TSH. A single bolus injection of TRH (500 micrograms) significantly stimulated prolactin secretion, but did not cause an increase in blood TSH levels (basal level, 1.2 microU ml-1 vs. 1.3 microU ml-1 30 min after injection). By contrast, TRH-induced TSH stimulation occurred after repeated injection of TRH for 4 consecutive days (basal level, 1.5 microU ml-1 vs. 5.6 microU ml-1 30 min after injection). Blood thyroid hormone concentrations were restored to normal levels after long-term administration of TRH. Other pituitary functions remained unchanged. A diagnosis of central hypothyroidism due to isolated TRH deficiency was made in this case, and the data presented here indicate that partial resistance of pituitary thyrotrophs to TRH may be associated with depression.

Cold Temperature↗

PubMed1991

Glucose affects the release of thyrotropin-releasing hormone from the rat hypothalamus.

We have attempted to elucidate the effect of glucose concentrations on the release of thyrotropin-releasing hormone (TRH), a brain neuropeptide possessing glucoregulatory function, from rat hypothalamic slices in vitro. Rat hypothalamic slices were preincubated for 60 min at 37 degrees C in Krebs-Ringer bicarbonate (KRB) buffer (pH 7.4) containing varying concentrations of glucose (10, 5, 2.5 and 1 mM), and then tissues were incubated in KRB buffer, followed by stimulation with 60 mM K+ or 1 mM ouabain. In addition, after inducing hypoglycemia by insulin administration in the rat, hypothalamic tissues were dissected out and preincubated in KRB buffer (10 mM glucose) and then incubated in fresh KRB buffer containing 1 mM ouabain. A decrease in the glucose concentration of incubation medium caused a dose-dependent decrease in both K(+)- and ouabain-stimulated TRH release from rat hypothalamic slices. Furthermore, the ouabain-stimulated TRH release from the hypothalamus of rats with insulin-induced hypoglycemia was significantly reduced (45% of control values; p less than 0.01). The present results indicate that in vitro and in vivo hypoglycemia resulted in a significant decrease in the release of TRH from the hypothalamus, suggesting that circulating glucose levels affect TRH release which, in turn, might be responsible for peripheral glucoregulation.

Animals↗

PubMed1991

A novel TRH analog, YM14673, stimulates intracellular signaling systems in the brain more potently than predicted by its pituitary actions.

YM14673, a novel analog of TRH, substituting the (oxo-azetidinyl)carbonyl moiety for the pyroglutamyl moiety of TRH, was synthesized and its brain action was evaluated using rat brain slices in vitro. The addition of YM14673 engendered significant and dose-dependent increases in cyclic AMP formation in the hypothalamus and inositol phosphates (IP) accumulation in the cerebellum. The actions of YM14673 did not statistically differ from those of TRH on brain tissues. However, YM14673 did not show a direct interference with TRH binding in the brain membranes. [3H]YM14673 underwent to the same extent the enzymatic degradation by type II pyroglutamyl aminopeptidase as did TRH. As compared with TRH, YM14673 had a lower activity with respect to stimulation of thyrotropin secretion and accumulation of IP in the anterior pituitaries. The data imply that YM14673 possessed potent stimulatory actions on brain intracellular signaling systems with weak hypophyseal activities. These actions of YM14673 were not due to a direct interference with brain TRH binding or a nature impervious to a TRH-degrading enzyme. The present study indicates that the larger doses of YM14673 than TRH can be used for medical treatment of neurological and neuromuscular disorders without strong influences on pituitary functions.

Animals↗

PubMed1991

Hypothyroidism inhibits the formation of inositol phosphate in response to carbachol in the striatum of adult rat.

The effects of hypothyroidism on the muscarinic cholinergic receptor-coupled inositol phospholipid hydrolysis in the adult rat brain were examined. Tissue slices of striatum, hippocampus, and cortex from either euthyroid or hypothyroid rats were labeled with [3H]myoinositol and incubated with carbachol, a muscarinic cholinergic agonist. In other experiments, crude plasma membranes of each brain region obtained from either euthyroid or hypothyroid rats were incubated with [3H]N-methylquinuclidinyl benzilate ([3H]NMeQNB), a muscarinic cholinergic antagonist, in the presence or absence of atropine. Carbachol produced a significant increase in [3H]inositol phosphate ([3H]IP) formation in each brain region in a dose dependent manner. Hypothyroidism caused a marked decrease in carbachol-stimulated [3H]IP formation in the striatum, whereas it did not affect the formation of [3H]IP in the cortex or hippocampus. In contrast, the affinity constant and the maximal binding of [3H]NMeQNB to plasma membranes in these regions were not changed by hypothyroidism. The present results suggest that thyroid hormones might participate in regulating the muscarinic cholinergic neurotransmission in the striatum of adult rat.

Animals↗

PubMed1990

Stimulation by a TRH precursor, TRH-Gly, of TSH and PRL secretion in rats: effect of starvation.

The hypophysial activities of a possible direct precursor of thyrotropin (TSH)-releasing hormone (TRH), TRH-Gly, were evaluated in estrogen, progesterone-primed rats under urethane anesthesia. Intravenous administration of TRH-Gly in doses of 2-200 micrograms caused a significant and dose-dependent increase in blood TSH and prolactin (PRL). The stimulatory activity of TRH-Gly was 170 to 400-times less potent than that of TRH. The lower potency was confirmed by the action of TRH-Gly on the anterior pituitary cells in vitro. In starved rats, TRH-Gly apparently stimulated TSH and PRL secretion in a dose-dependent manner, and the stimulatory activity increased in starved rats as compared to normal controls. TRH-Gly did not affect [3H-MeHis]TRH binding in pituitary plasma membranes. These data imply that large amounts of TRH-Gly may have significant biological activities and these are potentiated in the starved condition.

Animals↗