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V Strbák

Publications and source records attributed to V Strbák.

At least 19 recordsLinked to original sources

The effect of swelling on TRH and oxytocin secretion from hypothalamic structures.

1. Cell swelling induces exocytosis of material stored in secretory vesicles resulting in a secretory burst of peptidic hormones or enzymes from various types of cells including endocrine cells and neurons. We have previously shown that swelling-induced exocytosis possesses limited selectivity; hypotonic medium evokes TRH but not oxytocin release from hypothalamic paraventricular nucleus (PVN) and neurohypophysis (NH). 2. It is the aim of this study to ascertain whether the swelling-induced oxytocin secretion could be unmasked by the inhibition of specific osmotic response using Ca(2+)-free medium and GdCl(3), an inhibitor of stretch activated channels. 3. Oxytocin release from the PVN was stimulated by the hypotonic medium only in the presence of 50 or 100 microM GdCl(3.) Oxytocin release from supraoptic nucleus (SON) was also stimulated by the Ca(2+)-free hypotonic medium in the presence of GdCl(3). Oxytocin secretion from the NH was not stimulated even in the presence of GdCl(3), both in Ca(2+) containing and Ca(2+)-free medium. TRH response to swelling-inducing stimulus was not affected by the presence of GdCl(3). 4. An intranuclear oxytocin secretion to hyposmotic stimulation within the PVN and the SON could be unmasked by the inhibiting specific response by GdCl(3). At these conditions general secretory response to swelling-inducing stimuli emerged. Secretion of oxytocin from the NH was not affected by any of these treatments. 5. Peptides and proteins released after cell swelling can play an important role in the pathophysiology of ischemia and could be mediators of local or remote preconditioning. Disruption of mechanosensitive gating in magnocellular neurosecretory cells could result in an inadequate secretory response (e.g. stimulation instead of inhibition and vice versa) of hormones engaged in water and salt metabolism regulation.

Animals↗

Effect of neonatal streptozotocin and thyrotropin-releasing hormone treatments on insulin secretion in adult rats.

Neonatal STZ (nSTZ) treatment results in damage of pancreatic B-cells and in parallel depletion of insulin and TRH in the rat pancreas. The injury of B-cells is followed by spontaneous regeneration but dysregulation of the insulin response to glucose persists for the rest of life. Similar disturbance in insulin secretion was observed in mice with targeted TRH gene disruption. The aim of present study was to determine the role of the absence of pancreatic TRH during the perinatal period in the nSTZ model of impaired insulin secretion. Neonatal rats were injected with STZ (90 microg/g BW i.p.) and the effect of exogenous TRH (10 ng/g BW/day s.c. during the first week of life) on in vitro functions of pancreatic islets was studied at the age 12-14 weeks. RT-PCR was used for determination of prepro-TRH mRNA in isolated islets. Plasma was assayed for glucose and insulin, and isolated islets were used for determination of insulin release in vitro. The expression of prepro-TRH mRNA was only partially reduced in the islets of adult nSTZ rats when compared to controls. nSTZ rats had normal levels of plasma glucose and insulin but the islets of nSTZ rats failed to response by increased insulin secretion to stimulation with 16.7 mmol/l glucose or 50 mmol/l KCl. Perinatal TRH treatment enhanced basal insulin secretion in vitro in nSTZ animals of both sexes and partially restored the insulin response to glucose stimulation in nSTZ females.

Aging↗

Effect of immobilization on in vitro thyrotropin-releasing hormone release from brain septum in wild-type and corticotropin-releasing hormone knock-out mice.

There is considerable evidence linking alcohol consumption, sedation, and thyrotropin-releasing hormone (TRH) in the brain septum. We have shown that ethanol in clinically relevant concentrations can in vitro induce TRH release from the septum by a mechanism involving neuronal swelling. Corticotropin-releasing hormone-deficient (CRH-KO) mice serve as an interesting model to help us understand the role of CRH in the regulation of different neuroendocrine systems. The aim of this study was to compare TRH release activity in the brain septum at basal and stress conditions in CRH-KO mice and their wild-type (WT) littermates. Experimental mice were decapitated immediately or 3 h after single (2 h) or repeated (seven times for 2 h daily) immobilization stress. The brain septum was immediately cut out and incubated to measure basal-, ethanol-, and hyposmosis-stimulated TRH release in vitro. Ethanol in isosmotic medium or hyposmotic medium stimulated TRH release from mice septal explants from WT and CRH-KO mice. The response was disturbed immediately after immobilization and recovered 3 h later. Our results show that immobilization stress transiently affects the TRH system in brain septum. Inborn absence of CRH does not affect septal TRH and its response to ethanol before and 3 h after immobilization.

Animals↗

Cell swelling induced secretion of TRH by posterior pituitary, hypothalamic paraventricular nucleus and pancreatic islets: effect of L-canavanine.

The aims of this study were to test if ethanol induces thyrotropin-releasing hormone (TRH) secretion in vitro from the posterior pituitary and hypothalamic explants by a mechanism involving cell swelling, and to characterize the pathway of stimulated secretion. Ethanol, at a concentration of 80 mM, stimulated the release of TRH from the posterior pituitary, the hypothalamic paraventricular nucleus, the median eminence, and the brain septum, when administered only in isosmolar but not in hyperosmolar medium. This indicates the involvement of a cell swelling-inducing mechanism. L-canavanine in a concentration of 3 mM, increased the basal and hyposmosis-induced TRH secretion from the posterior pituitary and the paraventricular nucleus, and both basal and ethanol-induced TRH secretion from isolated pancreatic islets. This indicates the presence of both constitutive and regulatory secretory pathways. Our results suggest that cell swelling induces exocytosis from clathrin coated granules.

Animals↗

Body mass, plasma leptin, glucose, insulin and C-peptide in offspring of diabetic and non-diabetic mothers.

OBJECTIVE: The aim was to investigate the relationship between body mass index (BMI), plasma leptin, glucose, insulin and C-peptide levels in the offspring of diabetic mothers (DM) and non-diabetic healthy mothers (HM). DESIGN: Seventy-two offspring (37 girls and 35 boys, age 4-20 years) of DM were investigated in a prospective study. Those 14-16 years old (Tanner stage II-IV) were compared with age-matched offspring of HM (33 girls and 33 boys). RESULTS: BMI strongly correlated with plasma leptin concentration in the offspring of both DM and HM children. There were higher BMI and plasma leptin and glucose levels in DM than in HM children. There was no difference in plasma insulin or C-peptide levels between HM and age-matched DM children. There was a highly significant positive correlation between plasma leptin and C-peptide in boys of DM. CONCLUSIONS: The higher plasma leptin found in the offspring of DM reflects their higher BMI. A moderately high but still normal glycemia might be a preclinical sign of insulin resistance or other disturbance of glucoregulation.

Adolescent↗

The osmotic component of ethanol and urea action is critical for their immediate stimulation of thyrotropin-releasing hormone (TRH) release from rat brain septum.

There is considerable evidence linking alcohol consumption and sedation and TRH in the brain septum. Moreover, innate septal TRH concentration is inversely related to the degree of ethanol preference. Recently we demonstrated in rats that four-week ethanol drinking increased the septal TRH content by 50 %. We had shown previously that ethanol induces neuronal swelling, which is known to evoke the secretion of hormones, peptides and amino acids from various types of cells. We have therefore explored the effect of hyposmotic medium and of 80 and 160 mM ethanol and 80 mM urea (both permeant molecules) in isosmotic and hyperosmotic (preventing cell swelling) media on the in vitro release of TRH by the rat septum. Lowering medium osmolarity resulted in a hyposmolarity-related increase in TRH secretion. Both ethanol and urea stimulated TRH release only in isosmolar solution. Our data indicate that ethanol in clinically relevant concentrations can induce TRH release from the septum by a mechanism involving neuronal swelling.

Animals↗

Four-week ethanol drinking increases both thyrotropin-releasing hormone (TRH) release and content in rat pancreatic islets.

Ethanol exerts profound effects on the endocrine and exocrine pancreas. Some effects of chronic alcohol consumption on insulin secretion in response to glucose load are similar to those of TRH gene disruption. TRH is present in insulin-producing B-cells of the islets of Langerhans; its role in this location is still not fully explored. To examine the possible effect of long-term in vivo ethanol treatment on pancreatic TRH we compared three groups of rats: a 10% (wt:vol) ethanol-drinking group (E), absolute controls (AC) and pair-fed (PF) group with solid food intake corresponding to that of E. The fluidity of pancreatic membranes was not affected by chronic in vivo exposure of rats to ethanol, but was significantly decreased in PF group. Four-week treatment resulted in significantly higher TRH content in isolated islets of the E group and increased basal and 80 mM isotonic ethanol-induced secretion compared to AC and PF. Plasma levels of insulin, C-peptide, IGF-I, and glycemia were, however, not affected by ethanol treatment. Cell swelling, which can be induced by the presence of permeants (e.g. ethanol) in an isotonic extracellular medium, is a strong stimulus for secretion in various types of cells. In the present study, isosmotic ethanol (40, 80, and 160 mM) induced dose-dependent release of TRH and insulin from adult rat pancreatic islets in vitro. The same concentrations were not effective when applied in a hyperosmotic medium (addition of ethanol directly to the medium), thus indicating the participation of cell swelling in the ethanol-induced secretion. In conclusion, chronic ethanol treatment significantly affected pancreatic TRH and this effect might be mediated by cell swelling. The role of these changes in the profound effect of ethanol on the endocrine and exocrine pancreas remains to be established.

Animals↗

Regulation of hormone secretion by acute cell volume changes: Ca(2+)-independent hormone secretion.

Exocytosis of intravesicular material should help a cell meet a relative extracellular hyposmotic challenge by expanding the plasmalemma through fusion with vesicular membrane. Cell swelling evokes an immediate secretory burst of hormones stored in secretory vesicles with dynamics indistinguishable from those induced by specific secretagogues. Hormone secretion induced by cell swelling is not associated with a rise in cAMP, IP(3), or prostaglandins, and it is not depressed by inhibition of stretch mechano-receptors or aquaporin channels. In contrast to most types of regulated secretion, that induced by cell swelling in normal cells does not require a rise in intracellular Ca(2+) through opening L-type Ca(2+) channels. However, such Ca(2+) influx is essential for cell-swelling induced secretion in tumor-derived pituitary cells. Cell swelling induces universal secretion of exocytotic material. The response of cells specialized in osmoregulation is, however, different. Possible physiological significance: Consistent stimulation of secretion occurs with a 4% hyposmolar challenge. It is likely that fluctuations in osmotic pressure with resultant cell volume changes have a significant regulatory role in hormone secretion. Released hormones could also play an important role in the pathophysiology of ischemia. Exocytosis itself does not have an essential role in volume regulation.

Animals↗

Glucose stimulates and insulin inhibits release of pancreatic TRH in vitro.

OBJECTIVE: Pancreatic TRH is present in insulin-producing B-cells of the islets of Langerhans. There is fragmentary evidence that it may be involved in glucoregulation. The aim of our present study was to analyze how glucose and insulin affect TRH secretion by the pancreatic islets. DESIGN: Isolated pancreatic islets were incubated with different concentrations of glucose, insulin and glucagon, and TRH release was measured. RESULTS: In the present study, 6 and 12mmol/l d-glucose caused significant TRH release from isolated adult rat pancreatic islets when compared with that in the presence of the same concentrations of biologically ineffective l-glucose. Thirtymmol/l d-glucose was also ineffective, but this was not due to depression of secretion by hyperosmolarity since isosmotic compensation for the high glucose addition did not restore its stimulatory effect. Five micromol/l dibutyryl cyclic 3',5'-adenosine monophosphate (db-cAMP) increased both basal and glucose-stimulated TRH release, but this effect was not seen with 50micromol/l db-cAMP. Stimulation of phosphodiesterase by imidazole resulted in decreased basal but not glucose-stimulated release of TRH. Glucagon (10(-7)mol/l) did not affect either basal or glucose-stimulated release of TRH, while insulin (10(-7) and 10(-6)mol/l) inhibited both. CONCLUSION: Our present data showing that glucose stimulates and insulin inhibits pancreatic TRH release are compatible with the possibility that this substance may play a role in glucoregulation.

Animals↗

Comparison of pancreatic and hypophysiotropic TRH systems.

The thyrotropin-releasing hormone (TRH) is a molecule with widespread distribution through many organ systems. The function of TRH is probably not identical in each system so that TRH synthesis and secretion may be unique for each system under specific experimental conditions. The present study was designed to explore the common and diverse features of the regulation of TRH encoded with the same gene in two different organs: hypophysiotropic hypothalamus and pancreatic islets. During in vitro incubation, the TRH content in hypothalamic structures remained stable while that in isolated pancreatic islets increased sharply. In contrast to the pancreatic islets, exposure to different concentrations of D-glucose did not affect TRH release from the hypothalamic paraventricular nucleus or median eminence. This divergence in the regulation of the hypophysiotropic and pancreatic TRH systems may be related to differences in the role of TRH produced in these tissues.

Animals↗

Hypo-osmolarity stimulates and high sodium concentration inhibits thyrotropin-releasing hormone secretion from rat hypothalamus.

The hypothalamic paraventricular nucleus, representing cell bodies in which thyrotropin-releasing hormone is synthesized, and the median eminence, representing nerve terminals, were incubated in vitro. Various hypo- and hyperosmotic solutions were tested to determine osmotic sensitivity of thyrotropin-releasing hormone secretion. High KCl (56 mM) causing membrane depolarization was used as a non-specific control stimulus to induce thyrotropin-releasing hormone secretion. A 30% decrease of medium osmolarity (from 288 to 202 mOsmol/l) increased thyrotropin-releasing hormone secretion from both the paraventricular nucleus and median eminence. A 30% decrease of medium NaCl content by its replacement with choline chloride did not affect basal thyrotropin-releasing hormone secretion. Increasing medium osmolarity with biologically inactive L-glucose did not affect basal or KCl-induced thyrotropin-releasing hormone secretion from either structure. Medium made hyperosmotic (350-450 mOsmol/l) by increasing the NaCl concentration resulted in a dose-dependent decrease of basal thyrotropin-releasing hormone secretion and abolished KCl-induced thyrotropin-releasing hormone secretion. If an osmotically equivalent amount of choline chloride was substituted for NaCl, there was no effect on thyrotropin-releasing hormone secretion, indicating a specific action of Na+. This study indicates a specific sensitivity to high concentrations of Na+ ions of both thyrotropin-releasing hormone-producing parvocellular paraventricular neurons and thyrotropin-releasing hormone-containing nerve terminals in the median eminence.

Animals↗

Four-week ethanol intake decreases food intake and body weight but does not affect plasma leptin, corticosterone, and insulin levels in pubertal rats.

Long-term intake of ethanol decreases food intake and inhibits growth in experimental rats. The aim of this study was to determine the effect of 4-week oral ethanol ingestion on plasma leptin and adrenal function. Male 45-day-old Wistar rats were divided into three groups: absolute control (AC), ethanol (E) administered 10% (wt/vol) ethanol instead of tap water, and pair-fed (PF) given an amount of food corresponding to the food intake of E animals. E rats consumed less pelleted diet (74% cumulative total intake); however, this caloric deficit was compensated by ethanol ingestion. Net water intake in E animals was 76% of that in the control groups. The body growth of both E and PF rats was stunted compared with AC animals, but E rats were heavier than PF rats. The plasma leptin level was similar in E and AC and decreased in PF animals. There were no differences in plasma osmolality or glycemia among the three groups. Plasma insulin was decreased in PF compared with both AC and E rats. Plasma corticosterone was not affected by ethanol, but was increased in the food-restricted (PF) group. Although there were no differences in basal adrenal corticosterone production in vitro, there was a slightly higher response to corticotropin (ACTH) in E rats. We conclude that drinking 10% ethanol decreased the dietary intake and body growth. These changes were not mediated by plasma leptin changes. Although alcohol ingestion and its energy content theoretically normalized the total energy intake and prevented the decrease of plasma leptin, the growth of young rats was inhibited. Drinking 10% ethanol instead of tap water for 4 weeks did not stimulate basal adrenal activity.

Adrenal Glands↗

Long-term action of potassium bromide on the rat thyroid gland.

Male rats fed by a standard diet with determined of bromine and iodine content were exposed to a 133-day oral administration of KBr (100, 200, 400 mg Br-/l drinking water). Their thyroid glands showed increased growth of the epithelial cells reflected by a microfollicular rearrangement of the parenchyma due to proliferation of very small follicles with a low or zero content of colloid. Morphometric analysis of thyroids of Br(-)-exposed animals revealed a significant decrease in the volume of intrafollicular colloid and marked increase in the number of the smallest follicles (areas up to 100 and 100-300 micron 2). In addition, the nuclei of thyrocytes showed an increased number of mitoses. The vascularization was increased as well. In the blood plasma of the Br(-)-exposed animals the T4 concentration was significantly decreased in dependence on the bromine concentrations. Thyroglobulin immunoreactivity in the colloid of Br(-)-exposed animals decreased after administration of 400 mg Br-/l drinking water. Increasing concentrations of Br- in the drinking water caused an increased bromine concentration in the thyroid, a decreased iodine content and a decreased I/Br molar ratio. The changes in the rat thyroid caused by long-term administration of 100 mg Br-/l were similar to hyperplastic parenchymal goitre and were comparable to those induced in previous experiments by the same bromine concentration administered over a 16- and 66-day period respectively.

Administration, Oral↗

Chronic ethanol drinking and food deprivation affect rat hypothalamic-pituitary-thyroid axis and TRH in septum.

Because chronic ethanol ingestion may perturb thyroid function, we evaluated the effect of 4-wk of oral 10% ethanol ingestion on the hypothalamic-pituitary-thyroid (HPT) axis and septal thyrotropin-releasing hormone (TRH) in 200-g male Wistar rats. Animals were divided into three groups: absolute control receiving tap water and food ad libitum; ethanol group receiving food ad libitum and 10% ethanol as the sole source of drinking fluid; pair-fed group receiving tap water and an amount of food corresponding to the consumption of ethanol group. After 4-wk of treatment, the body weight of the ethanol group was 7% and of the pair-fed rats 19% lower than that of the absolute controls. Both chronic ethanol treatment and food deprivation produced a decrease in plasma thyroid-stimulating hormone (TSH). Pair-fed rats also had a lower plasma T3. Type I iodothyronine 5'-deiodinase activity in the liver was increased in the pair-fed and even more in the ethanol-treated group. The content and secretion in vitro of TRH from the hypothalamic paraventricular nucleus and median eminence were unchanged. TRH content in the septum was increased in both the ethanol and pair-fed groups. TRH secretion from the septum in vitro was lower in the pair-fed, but unchanged in the ethanol group. These data suggest that 4-wk of peroral ethanol intake affects thyroid function mostly at the extrahypothalamic level and that there is a contribution of concomitant food deprivation. Both ethanol treatment and food deprivation increased TRH content in the septum.

Alcoholism↗

Thyroid hormone receptor occupancy and biological effects of 3,5,3,-L-triiodothyronine (T3) in GH4C1 rat pituitary tumour cells.

The GH4C1 pituitary cell line, an excellent model for a thyroid hormone action study, was used for determination of the relationship between thyroid hormone receptor occupancy and intensity of cell proliferation, prolactin (PRL) production, thyrotropin (TSH) inhibition and 3,5,3,-L-triiodothyronine (T3) receptor down-regulation. Nuclear receptor population was progressively occupied by T3 in concentrations ranging from 0.025 to 10.0 nM T3. Bmax ranged from 0.029 fmol/10(6) cells at the lowest T3 concentration to Bmax = 12.51 fmol/10(6) cells at the highest concentration. Each of the observed biological events is operative within distinct dose-response ranges in cultured GH4C1 cells. The maximal biological response (except the TSH inhibition and T3 receptor down-regulation) does not require the occupation of the whole nuclear receptor population by T3 and the intensity of none of the responses studied was directly proportional to thyroid hormone receptor occupancy.

Animals↗

Hyposmolar medium and ethanol in isosmotic solution induce the release of thyrotropin-releasing hormone (TRH) by isolated rat pancreatic islets.

Cell swelling induced by hypotonic medium or small isotonic permeant molecules results in an immediate secretory response in various types of cells. We have expanded exploration of this phenomenon by examining the effect of either isotonic ethanol or hyposmotic medium on the release of TRH by freshly isolated islets of Langerhans in static incubation and perifusion. Ethanol (40, 80 or 160 mM in isotonic solution) dose-dependently evoked the release of TRH by statically incubated islets. The dynamics of TRH release induced by 80 mM isotonic ethanol or 30% hypotonic medium were similar to those induced by 50 mM KCl, with the highest secretion rate during the first 5 min of incubation irrespective of the duration of stimulation. Ca2+ depletion of the incubation medium abolished the response to 50 mM KCl but did not diminish the response to 80 mM isotonic ethanol. We conclude that osmotic stimuli known to induce cell swelling also induce release of TRH by isolated pancreatic islets.

Animals↗

Both iso- and hyperosmotic ethanol stimulate release of hypothalamic thyrotropin-releasing hormone despite opposite effect on neuron volume.

Previous studies have indicated that isosmolar, but not hyperosmolar, ethanol induces in vitro gonadotropin-releasing hormone secretion from the basal hypothalamus, presumably by causing cell swelling. Moreover, ethanol reduces secretion of another hypothalamic neuropeptide vasopressin. We have studied the acute effect of ethanol on specific hypophysiotropic basal and K+-stimulated thyrotropin-releasing hormone secretion in vitro especially in relation to cell swelling. Isosmotic 40-160 mM ethanol increased thyrotropin-releasing hormone release from the hypothalamic paraventricular nucleus and median eminence in a dose-dependent manner. Both a 30% decrease of osmolarity and isosmotic 80 mM ethanol induced 12% swelling of hypothalamic neurons. Hyperosmotic 80 mM or 160 mM ethanol induced release of thyrotropin-releasing hormone from both hypothalamic structures but did not cause cell swelling (80 mM) or even induced cell shrinkage (160 mM). Depletion of medium Ca2+ did not affect thyrotropin-releasing hormone secretion caused by either isosmotic or hyperosmotic ethanol. Our data indicate that both iso- and hyperosmotic ethanol stimulated release of hypophysiotropic thyrotropin-releasing hormone despite opposite effects on neuron volume. The mechanism of ethanol action appears complex and variable depending on the type of cell and neuropeptide affected.

Animals↗