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Biomedical subjects

G Csaba

Publications and source records attributed to G Csaba.

At least 37 records · Page 2Linked to original sources

Molecules acting on receptor level at weaning, durably influence liver glucocorticoid receptors.

In the experiments the effect of late hormonal imprinting to the liver glucocorticoid receptors were studied. Three-week-old (weanling) female rats were treated with five molecules acting at receptor level and four weeks later receptor kinetic analysis was done on liver glucocorticoid receptors. The tricyclic antidepressant, histamine and serotonin receptor blocker mianserin positively influenced receptor density and negatively receptor affinity. Vitamin D3 and the environmental pollutant benzpyrene elevated receptor density. Mifepristone (RU 486) which is bound by progesterone- and glucorticoid-receptor without postreceptorial effects was ineffective as well, as the H1 receptor blocker chlorpheniramine. The results demonstrate that receptor-level-acting foreign molecules can durably influence the binding capacity of glucocorticoid receptors, however, this is not a general phenomenon and it is not dependent on the type of receptors (membrane or cytosol). Those molecules were effective which 1. have receptor in the same receptor family (vitamin D3) and have postreceptorial effect, or 2. have a structure similar to steroids (benzpyrene) or 3. deeply influenced steroid receptors in earlier experiments (mianserin). This effect should be considered before administering such type of medicaments.

Animals↗

Influence of acute stress on the triiodothyronine (T3) and serotonin content of rat's immune cells.

Stress caused by 48 h food and water deprivation provoked significant changes in T3 and serotonin content of lymphocytes. The concentration of these hormones decreased in the last hour of stress. However, 48 h later there was no difference between the hormone content of immune cells of stressed and control animals. Since in earlier experiments three weeks after exposed to stress a significant difference between the control and stressed animals was found, this means that an imprinting-like phenomenon happened with consequences manifested later. The most sensitive cells to acute stress are lymphocytes, however the imprinting influences all types of of the immune cells.

Animals↗

Effect of treatment at weaning with the serotonin antagonist mianserin on the brain serotonin and cerebrospinal fluid nocistatin level of adult female rats: a case of late imprinting.

Four weeks old (weanling) female rats were treated with the tricyclic antidepressant and histamine/serotonin receptor blocker mianserin for studying its faulty hormonal imprinting effect. Measurements were done four months later. Brain serotonin levels significantly decreased in four regions (hippocampus, hypothalamus, striatum and brainstem), without any change in the cortex. Sexual activity of the treated and control rats was similar. Cerebrospinal fluid nocistatin level was one magnitude higher in the treated rats, than in the controls. The density of uterine estrogen receptors was significantly reduced, while binding capacity of glucocorticoid receptors of liver and thymus remained at control level. The results call attention to the possibility of 1. a broad spectrum imprinting at the time of weaning by a receptor level acting non-hormone molecule 2. imprinting of the brain in a non-neonatal period of life and 3. a very durable (lifelong?) effect of the late imprinting with an antidepressant.

Animals↗

Prolonged impact of five imprinters on the serotonin content of white blood cells and mast cells of weanling rats: outstanding effect of benzpyrene and chlorpheniramine.

In previous experiments, treatment at weaning or adult age with endorphin, serotonin or an antihistamine (late hormonal imprinting) durably influenced the serotonin content of white blood cells and mast cells of rat. In the present experiments, five molecule (approved imprinters in other indexes) were studied for imprinting effect of immune cells, 3 weeks after a single treatment at weaning. Three steroid hormone-like molecule (vitamin D3, mifepristone and dexamethasone) were ineffective (except dexamethasone in 1/4 indexes), while benzpyrene (aromatic hydrocarbon) and chlorpheniramine (H1-receptor blocker antihistamine) were highly effective (5/6 and 4/4 respectively). The results indicate: (1) a prolonged (late imprinting) effect of a single treatment with certain molecules acting at receptor level; (2) non-generality of late imprinting, and (3) the very extensive effects of benzpyrene, which in earlier experiments was one of the strongest imprinter at receptorial and behavioral level at any periods of life studied.

Animals↗

Immunologically demonstrable hormones and hormone-like molecules in rat white blood cells and mast cells.

The presence or absence of four biologically active hormone or hormone-like molecules was studied in rat immune cells using specific antibodies with flow cytometry and confocal microscopy. Epidermal growth factor (EGF) was not demonstrable at all, digoxin was present only in blood lymphocytes, and insulin was found in the monocyte-macrophage-granulocyte group in peritoneal fluid and thymic lymphocytes. Immunologically demonstrable triiodothyronine (T3) was present in all cells studied (lymphocytes, mast cells and monocyte-macrophage-granulocytes in peritoneal fluid and blood, and thymic lymphocytes). While there is no explanation of the presence of digoxin and insulin, it is assumed that T3 is an extrathyroidal source of the hormone that is needed for maintaining cell proliferation and normal status in the immune system, particularly as it is absent in the case of transitional or durable thyroid deficiency.

Animals↗

Presence and localization of epidermal growth factor (EGF)- and EGF-receptor-like immunoreactivity in Tetrahymena.

The presence of EGF- and EGF-receptor-like immunoreactivity in Tetrahymena was studied with the help of FITC-labelled monoclonal antibodies, using flow cytometry and confocal microscopy. Tetrahymena has endogeneous EGF and treatment with it significantly increases the hormone content of the cells. The hormone is diffusely localized, particularly in the cytopharynx, where it forms a structure larger than 10 microm. EGF-receptors are also demonstrable, particularly in the cortical region in connection with cilia, and EGF treatment significantly enhances cortical fluorescence. The relationships between these observations and literary data on the effects of EGF in Tetrahymena are discussed.

Animals↗

Endorphin excess at weaning durably influences sexual activity, uterine estrogen receptor's binding capacity and brain serotonin level of female rats.

Perinatally, the first encounter between the maturing receptor and its target hormone results in hormonal imprinting, which adjusts the binding capacity of the receptor for life. In the presence of an excess of the target hormone or foreign molecules than can be bound by the receptor, faulty imprinting carries life-long consequences. In cytogenic organs, imprinting could also be provoked in other periods of life (late imprinting). Imprinting also durably influences the production of the imprinter and related hormones. In the present study, single beta-endorphin doses was given to three-week old female rats at 3 microg/animal, and the serotonin in five brain regions (frontal cortex, striatum, hippocampus, hypothalamus and brain stem) and uterine estrogen receptor content were determined, thymic glucocorticoid receptor binding capacity was measured, and sexual behavior was tested at five months of age. Brain serotonin levels highly significantly decreased, while sexual activity (Meyerson index and lordosis quotient) increased. At the same time, uterine estrogen receptor affinity decreased. There was no change in receptor binding capacity in the thymus. We will go on to discuss interrelations between the results. The experiments demonstrate that a non-perinatal treatment with a molecule acting at receptor level (late imprinting) can also lastingly influence various indexes in non-cytogenic organs. The results call attention to the possible long-lasting influence of an endorphin surge (caused, for example, by pain) on brain serotonin content and sexual behavior.

Animals↗

Effect of single neonatal or repeated benzpyrene exposure on the serotonin content of immune cells in young male rats.

In earlier experiments single benzpyrene treatment of newborn rats caused strong alterations in the endorphin content of adult rats' immune cells. In the present experiments young (4-6 weeks old) male rats were studied for demonstrating the effect of the single neonatal or repeated (neonatally and at weanling) benzpyrene exposure on the serotonin content of immune cells (blood lymphocytes, monocytes, granulocytes; peritoneal fluid lymphocytes, mast cells, monocytes and granulocytes, thymic lymphocytes). Flow cytometric analysis showed that 50 microg benzpyrene treatment of five-week-old animals was ineffective after 5 days and this was the situation four weeks after single neonatal (20 microg) benzpyrene exposure. However, the repeated treatment of neonatally benzpyrene exposed 4 weeks old animals after 5 days resulted in elevated blood and thymic lymphocyte serotonin amount and in one index (peritoneal monocyte-granulocyte group) reduced serotonin content. This means that neonatal benzpyrene treatment does not influence directly the serotonin content (production or transport) of immune cells (unlike to the endorphin content) however, sensitizes them to a following benzpyrene exposure. The results widen the list of harmful effects (influencing steroid receptor binding, sexual behavior and immune cells' endorphin content) of perinatal benzpyrene exposure.

Animals↗

Impact of single neonatal serotonin treatment (hormonal imprinting) on the brain serotonin content and sexual behavior of adult rats.

Hormonal imprinting takes place perinatally at the first encounter between the developing receptor and its target hormone. As a consequence of imprinting the receptor accomplishes its maturation and reaches the binding capacity characteristic to the adult age. In the excess of target hormone or presence of molecules similar to the target hormone, which are able to bind to the unmatured receptors, faulty imprinting develops with life-long consequences. At present, serotonin was given to neonatal rats and their sexual activity, brain serotonin level and steroid receptor's binding capacity was measured in adult age. Brain serotonin level was significantly reduced in male's striatum and parallel with this, male's sexual activity significantly increased. In other regions of the male brain (prefrontal cortex, hypothalamus, hippocampus) there was a statistically non-significant tendency for a decrease in serotonin level. No significant differences were detected in female brain values, and there was only slight change in female's sexual activity. There was also no change in the binding capacity of thymic glucocorticoid and uterine estrogen receptors. The experiments call attention to the possibility of perinatal imprinting by a neurotransmitter causing changes in brain neurotransmitter level for life, which is manifested in altered sexual activity.

Animals↗

Effect of neonatal beta-endorphin imprinting on sexual behavior and brain serotonin level in adult rats.

A single dose (3 microg) beta-endorphin was administered to newborn female and male rats (hormonal imprinting). In adult age (at 5 months) sexual behavior, steroid hormone binding capacity and brain serotonin content was studied. Females' sexual activity (lordosis quotient) significantly decreased and more animals protested against mounting (ratio of kicking and crying 21/24 vs. 8/24; p < 0.001). Males' sexual activity did not change, however more males were aggressive (4/10 vs. 1/10). Uterine estrogen receptor density significantly increased and affinity decreased. There was no change in the binding capacity of thymic glucocorticoid receptors. In the brain, five regions were studied for serotonin content. There was a gender difference in serotonin level and the intragroup differences were also high. In the endorphin treated males the serotonin level was significantly lower than in the controls. In the endorphin treated females the intragroup scattering has been significantly reduced. Nociceptin content of the cerebrospinal fluid was not changed. The experiments call attention to the possibility of adjustment of sexual and behavioral sphere by the individually different endorphin surge during labor.

Aggression↗

Prolonged effect of a single serotonin treatment in adult age on the serotonin and histamine content of white blood cells and mast cells of rats.

Hormonal imprinting was provoked by serotonin treatment in adult age. Three weeks after treatment with 100 microg serotonin, the serotonin and histamine content of peritoneal cells (mast cells, lymphocytes and the monocyte-macrophage-granulocyte group), white blood cells (lymphocytes, granulocytes and monocytes) and thymic lymphocytes was studied by flow cytometry. The content of both amines was significantly higher in the mast cells of males and lower in females. Blood lymphocytes contained a higher serotonin and histamine level in males, and a lower serotonin level in females. The peritoneal monocyte-macrophage-granulocyte group contained less serotonin in both males and females. Thymocytes contained higher levels of both amines in females and higher histamine level in males. The experiments demonstrate that a single treatment at adult age can provoke imprinting, which alters-in the present case-the serotonin and histamine content of immune cells durably.

Age Factors↗

H1-receptor blocker antihistamine, terfenadine durably influences the glucocorticoid receptor, and lymphocyte histamine content of weanling rats.

Hormonal imprinting takes place perinatally when a hormone and its maturing target receptor meet. As a consequence of imprinting the receptor accomplishes its maturation reaching the binding capacity characteristic to the adult age. In this critical period the presence of foreign molecules which are able to bind to the receptor can cause faulty imprinting with life-long consequences. In the recent years it was cleared that not only receptors are influenced by faulty imprinting, however, also the hormone production of the given cell. In addition imprinting was provoked at non-perinatal periods (adolescence and adult age) in cytogenic organs. In the present experiment the prolonged effect of a non-perinatal imprinting by an antihistamine to the histamine content of white blood cells and glucocorticoid receptors of liver and thymus was studied. Two weeks after 3-day terfenadine treatment at weaning, flow cytometry of peritoneal cells and blood lymphocytes for histamine, and receptor kinetic analysis of dexamethasone binding were done. Histamine content of blood lymphocytes and glucocorticoid receptor density of liver cells were significantly decreased. This means that a short treatment with a H(1)-receptor blocker antihistamine durably influences physiological indexes which were not known till now. This means that not only the acute effects, but the prolonged side-effects must be considered.

Animals↗

Prolonged effect of the tricyclic antidepressant, mianserin on the serotonin and histamine content of young rats' white blood cells and mast cells. A case of late-imprinting.

Perinatal encounter of a hormone and its developing target receptor sets the receptor-hormone-signal transduction complex for life (hormonal imprinting). In this critical period excess of the appropriate hormone or foreign molecules able to bind the receptor can cause faulty imprinting with life-long consequences. At present the imprinter effect of a molecule bound by receptor was studied in female rats at weaning. Histamine and serotonin content of blood lymphocytes and peritoneal cells (lymphocytes, mast cells and the monocyte-granulocyte-macrophage group) was measured by flow cytometry three weeks after three days treatment of three-week-old rats with the histamine and serotonin antagonist tricyclic antidepressant, mianserin. The histamine content was dramatically elevated in each cell type except blood lymphocytes. The serotonin content was also elevated in peritoneal mast cells and decreased in peritoneal lymphocytes. Considering that the measurement was done three weeks after treatment, the results call attention to the long-lasting effect of a molecule acting at receptorial level.

Animals↗

Endorphin content of white blood cells and peritoneal cells in neonatally benzpyrene treated adult rats.

White blood cells of rats (lymphocytes, monocytes, macrophages, granulocytes and mast cells) contain beta-endorphin. Two months after a single neonatal benzpyrene treatment (imprinting) there is an elevated level of immunoreactive endorphin in the blood and peritoneal cells of female animals and blood cells of males. The endorphin content decreased in the peritoneal cells of males. In the blood, the granulocytes of female, and the lymphocytes of male rats contained the highest amount of endorphin. In the peritoneal fluid also the granulocytes of females contained the highest amount of endorphin, in contrast to males, where the endorphin content of cells decreased and the lowest level of it was present in the lymphocytes. The experiments justify that benzpyrene treatment can durably influence endorphin levels of white blood cells and gives new data to the already known lifelong health destroying effects of perinatal benzpyrene exposition (alterations of hormone receptor binding capacity and sexual behavior).

Age Factors↗

Induction of melatonin synthesis in Tetrahymena pyriformis by hormonal imprinting--a unicellular "factory" of the indoleamine.

Melatonin is present in Tetrahymena and its synthesis can be enhanced by pretreatment (imprinting) with melatonin. Two days after imprinting melatonin level is elevated in the cells and more elevated in the supematant. Such a minute quantity, as 10(-12) M melatonin for 1 hour is able to provoke imprinting, however the effect is more expressed using 10(-6) M. Maintenance in light conditions further elevated the amount of melatonin in the cells and supematant alike, related to the melatonin content of cells kept in darkness. The experiments call attention to the light-sensitivity of imprinting-provoked melatonin production in Tetrahymena and to the possibility of using this property for important physiological functions in higher grades of phylogeny.

Animals↗

Chemotactic-range-fitting of amino acids and its correlations to physicochemical parameters in Tetrahymena pyriformis--evolutionary consequences.

Amino acids are considered the oldest organic substances of the prebiotic evolution. Chemotactic effects of amino acid L-isomers investigated in the protozoan model Tetrahymena show that the chemotactic properties of amino acids are complex and depend on multiple physicochemical characteristics of the investigated ligands. The range of effectiveness is significantly wider for chemoattractant ligands than for chemorepellent ones. This phenomenon provides the basis of the "chemotactic-range-fitting" theory. The validity of this theory is supported by a decreased pK (-COOH), an increased pK (-NH2), and a decrease in solvent exposed areas and hydropathy indexes in chemoattractant amino acids compared to chemorepellent ones. Chemotactic selection has proven the activity of long-term (I, H, T) and short-term (P, A, Q, S) selector amino acids and their characteristic diversities in values of the pK and SEA (surface exposed area). Comprehensive studies of the chemotaxis data with the results of consensus analysis of amino acids suggests that chemotactic activity was one of the most primordial physiological activities and had a prospective significance not only in the molecular evolution of ligands, but also in the evolution of signalling.

Amino Acids↗

Melatonin in the unicellular Tetrahymena pyriformis: effects of different lighting conditions.

Melatonin content in the cellular fraction and medium of Tetrahymena pyriformis GL cultures was measured at different time points of light and dark exposures. Tetrahymena produced, stored and secreted immunoreactive melatonin, which in displacement and HPLC studies, behaved like synthetic melatonin. There was not a continuous secretion of melatonin produced by the cells. In contrast to this, storage of melatonin was observed, which was more expressed in dark conditions. Prolonged light exposure suppressed melatonin production and secretion alike, however it did not block it completely.

Animals↗

Beta-endorphin in granulocytes.

The literature indicates that beta-endorphin can be found in the mononuclear cells of peripheral blood. In the present experiments the endorphin content of granulocytes was studied, compared to lymphocytes as reference cells. Granulocytes as well, as lymphocytes contain endorphin. The granulocytes' endorphin content is much higher. Both lymphocytes and granulocytes are also able to take up endorphin from the milieu.

Animals↗