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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
PubMed2001

Effect of tamoxifen treatment at adolescent age on the sexual behaviour and steroid hormone receptor binding of adult female rats.

Hormonal imprinting takes place perinatally, at the first encounter between the target hormone and its developing receptor. However, there is a secondary critical period of imprinting at puberty. In these periods molecules similar to the hormones (members of the same hormone family, antagonists, certain environmental pollutants, etc.) can cause faulty imprinting with lifelong consequences. In the present experiments 5+2 days of tamoxifen treatment (120 microg/day) at adolescent age dramatically (from approx. 40% to 10%) reduced the sexual activity (Meyerson index and lordosis quotient) of female rats, soon after the finishment of the treatment and between four to six weeks after treatment. Similar results were observed in animals neonatally treated with allylestrenol and tamoxifen treated at puberty. Thymic glucocorticoid receptor and uterine estrogen receptor binding capacity were not influenced.

Aging↗
PubMed2000

Effect of neonatal treatment with mifepristone or tamoxifen on the binding capacity of the thymic glucocorticoid or uterine estrogen receptor of adult rats: data on the mechanism of hormonal imprinting.

For studying the mechanism of perinatal hormonal imprinting newborn rats were treated with a single injection of the antihormones, mifepristone (RU486) or tamoxifen (100 microg each). Glucocorticoid receptors of thymi of 6 weeks old male and female, and uterine estrogen receptors of 2 months old female rats were studied for dexamethasone or estradiol binding, respectively. Tamoxifen caused faulty imprinting both in the thymic and uterine receptors, increasing affinity and density of males, and decreasing females' glucocorticoid receptors as well, as decreasing the density of uterine estradiol receptors. Neonatal mifepristone treatment was indifferent to the thymus, and decreasing to density of uterine estrogen receptors. Males' body weight significantly decreased 6 weeks after tamoxifen treatment. The results suggest that imprinting can not be provoked by a molecule (hormone antagonist) which can bind to the receptor without any postreceptorial events (mifepristone/glucocorticoid receptor), in the presence of some postreceptorial effects the reaction takes place, however the strongest reaction can be observed by the hormone analogue (tamoxifen) with postreceptorial (agonist) effect, not considering that the receptor is the direct target of the molecule or a cross-reaction is present.

Animals↗
PubMed2000

Insulin uptake, localization and production in previously insulin treated and untreated Tetrahymena. Data on the mechanism of hormonal imprinting.

Confocal microscopic experiments demonstrate the presence of insulin in Tetrahymena, observed also in earlier experiments. However, there is a broad spectrum of insulin-containing cells from the immunocytochemically insulin-free, to the strongly antibody-reactive ones. During 1 h of insulin treatment (imprinting) the cells gradually bind and take up insulin, and the process is slow. One minute after the start of treatment there is not difference in the number of insulin antibody-reactive cells and amount of insulin. After 5 or 10 min the cells bind and contain more insulin and after 1 h most of the cells are densely packed with the insulin antibody-reactive material. Insulin imprinting accelerates binding and uptake alike: 48 h after imprinting and 1 min after the start of the second treatment, more insulin is present on the surface and inside the cells, than after 10 min in the first-time treated cells. Theoretically, this effect of hormonal imprinting helps to maintain the species by facilitating molecular recognition and binding as well as uptake of useful molecules. The experiments also support previous observations on the parallel receptor-evoking (strengthening) and hormone-producing effect of hormonal imprinting.

Animals↗
PubMed2000

Effect of glucosphingolipid synthesis inhibitor (PPMP and PDMP) treatment on Tetrahymena pyriformis: data on the evolution of the signaling system.

1-Phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP) are structural analogues of ceramide; inhibiting UDP-glucose : ceramide glucosyltransferase. After treatment with these synthetic ceramide analogues the expression of glucosphingolipid decreases, while ceramide and sphingomyelin levels increase in the cells of higher eukaryotes. In the unicellular Tetrahymena pyriformis, treatment with PDMP (10-20 microM) and PPMP (40-80 microM) influenced the synthesis of galactose, glucosamine and mannose-containing lipids. On the whole the amount of these lipids was reduced, but new galactose and glucosamine-containing lipids appeared (the exact structures of these lipids were not characterized). Incorporation of (32)P into phosphatidylethanolamine (PE) and phosphatidic acid (PA) was decreased significantly; however the amount of inositol phospholipids were increased. The incorporation of 3H-serine into phosphatidylserine was abolished, but incorporation into sphingomyelin and ceramide was increased. The cytoskeletal elements (silver line system) were disturbed on the basis of scanning electron microscopic pictures. The TRITC-Con A binding and the morphology of the cells were influenced as revealed by confocal laser scanning microscopic analyses. In contrast to higher eukaryotes, in Tetrahymena the shorter fatty acyl chain variant (PDMP) proved to be more effective in each of the examined parameters, while the longer chain variants (PPMP) had milder activity.

Animals↗
PubMed2000

Presence, uptake and localization of an immunoreactively interleukin 6 (IL-6)-like molecule in Tetrahymena pyriformis.

The unicellular Tetrahymena and its medium contain immunoreactively interleukin 6 (IL-6)-like molecules (hereinafter IL-6) in a measurable quantity in the 24 h-old cultures. This protozoan takes up exogenously supplied IL-6 very quickly, and this can be found in similar amounts in both the cells and the media after 1 h. After 24 h (48 h cultures), an equal amount of IL-6 is present in the control and IL-6-treated cells and their media. By 120 h, cells which have not had their medium changed retained the same quantity of IL-6 as the control; however less than half was found in IL-6-treated cells. In the medium of 120 h-old cultures, there was a reduction of IL-6 content relative to the 24 h content in the control; however, in the IL-6-treated cell culture medium, less than half of the level in the controls was found. Confocal microscopy demonstrated the localization of IL-6 in/on the oral apparatus and basal bodies, and the nuclear envelope also showed moderate labelling. IL-6 antibody binding was enhanced after IL-6 pretreatment (hormonal imprinting). The experiments call attention to the presence of an IL-6-like molecule and its uptake at a very low level of phylogeny.

Animals↗
PubMed2000

Chemotactic selection of Tetrahymena pyriformis GL induced with histamine, di-iodotyrosine or insulin.

It has been hypothesized that in phylogeny the encounter between potential signalling molecules and the continously changing cell membrane could result in the formation of a ligand specific receptor. This chemical (hormonal) imprinting is then transmitted to the progeny generations. It is, however, very difficult to know whether the selection of cells with receptor-like patterns or amplification of complete receptor-like patterns led to the formation of the receptor-hormone complex. The new technique of 'chemotactic selection provides a physiological response-guided selection of cells. It also enables the testing of subpopulations with the characteristic selector ligand. We show here that of three chemotactic ligands (histamine, di-iodotyrosine (T2) and human insulin), insulin and T2 selected subpopulations express a significantly high chemotactic response. Since the control medium has a selector capacity itself, we introduced a chemotactic selection coefficient (Chsel) which facilitates the comparison of all groups. Using this factor we found that insulin (Chsel = 1.57), functions as a strong selector and T2 (Chsel = 0.98), was a weak selector. Morphometric evaluation of the cells showed a good correlation between chemotactic responsiveness and morphometric characteristics of subpopulations selected with insulin and histamine. T2 data suggest that the long lasting responsiveness is not general, but might be subpopulation specific.

Animals↗
PubMed2000

Influence of a single treatment with vitamin E or K (hormonal imprinting) of neonatal rats on the sexual behavior of adults.

The effect of a single neonatal treatment (imprinting) with vitamin E or vitamin K1 on the sexual activity of three-month old rats, was studied. In female animals vitamin E treatment significantly lowered the Meyerson index and lordosis quotient, among males there were significantly more inactive animals and no multiple ejaculations could be observed. Vitamin K1 treatment caused only slight changes in the same direction, in both sexes. Considering also earlier results concerning vitamin A and D neonatal treatments (alterations in receptor binding capacity, sex hormone levels and sexual behavior), and receptorial changes caused by neonatal vitamin E and K1 treatments, the present experiment also calls attention to the lifelong effects of perinatal treatment with lipid soluble vitamins.

Animals↗
PubMed2000

A study of the liver glucocorticoid receptor binding capacity in newborn rat.

The binding capacity of newborn and adult rat liver glucocorticoid receptors was compared, using receptor kinetic analysis. Neonatal receptors have (non-significantly) lower affinity and significantly less density to dexamethasone than adult ones. However, the neonatal binding is specific and there is no qualitative difference from the adult one.

Aging↗
PubMed1999

Prolonged elevation of insulin content in the unicellular tetrahymena after insulin treatment: induction of insulin production or storage?

In the unicellular organism, Tetrahymena, the first encounter with an exogeneously given hormone results in hormonal imprinting. This causes an increase of the binding capacity of receptors and the production of the appropriate hormone in the progeny generations of the treated cell. In the present experiments the quantity (using radioimmunoassay) and localization (using confocal laser scanning microscopy) of the immunologically insulin-like material (hereafter insulin) were studied for 10 days after 4 h or 24 h 10(-6) M insulin treatment (hormonal imprinting). Forty-eight hours after both insulin treatments a high quantity of insulin was present in the cells. This value was also significantly increased after 96 h. After 8 days the difference to the control was significant only in the 24 h treated group. Confocal microscopy (using antibody to pig insulin) localized insulin in the cell body. The oral field contained extremely high quantities of the endogeneous hormone. Insulin treatment (after 48 and 96 h) caused an elevation of insulin content in general, and specific accumulation in the posterior sections of the cell, around the nucleus and in the periphery were observed. Ten days after both treatments only the peripheral region of the cell body and the ciliary row contained more insulin than the control. This means that after insulin treatment the quantity of insulin increases for a lengthy time period which is followed by the expression of insulin in the peripheral region. Insulin contained by Tetrahymena 48 h after imprinting stimulated glucose uptake of rat diaphragm.

Animals↗
PubMed1999

Localization of beta-endorphin in tetrahymena by confocal microscopy. Induction of the prolonged production of the hormone by hormonal imprinting.

The unicellular Tetrahymena has hormone receptors and hormones which are characteristic of higher vertebrates, as well as similar signal transduction pathways. In the present experiments, immunocytochemistry and confocal microscopy were used to study the presence and localization of beta-endorphin in Tetrahymena pyriformis GL. Endorphin (or endorphin-like material) was localized in the cortical structures, oral field, cilia and nuclear envelope. One-hour treatment with beta-endorphin ('hormonal imprinting') increased the presence of immunocytochemically demonstrable endorphin immediately and after 24 h, and was especially strong after 96 h of treatment. Simultaneous treatment with naloxone, an opioid antagonist, did not inhibit endorphin effect, but had an additive effect on endorphin production. Naloxone alone induced a very intensive accumulation of endorphin 96 h after treatment. The results support the possibility of a hormone production being induced by the imprinting procedure, but the imprinter-like effect of naloxone also points to the importance in this case of non-discriminatory receptors also being involved in the process.

Animals↗
PubMed1999

Effect of perinatal synthetic steroid hormone (allylestrenol, diethylstilbestrol) treatment (hormonal imprinting) on the bone mineralization of the adult male and female rat.

Neonatal treatment with allylestrenol or diethylstilbestrol (DES) reduced the bone mineral content (BMC/bw) of the adult (four months old) female rats, without influencing bone mineral density (BMD/bw). In males these neonatal treatments elevated BMC and BMD alike. Ovariectomy alone decreased BMC and BMD alike; however the neonatal hormone treatments did not influence this reduced value. Ovariectomy of two months old animals increased body weight without the influence of neonatal hormone treatments. In adult males, the body weight was reduced significantly by neonatal DES and non-significantly by neonatal allylestrenol treatment. The experiments call attention to the possible human bone-effects of allylestrenol, which was used in the last decades as medication protecting endangered pregnancies.

Absorptiometry, Photon↗
PubMed1999

Effect of single neonatal vitamin K1 treatment (imprinting) on the binding capacity of thymic glucocorticoid and uterine estrogen receptors of adolescent and adult rats.

Neonatal single treatment with vitamin K1 (50 microg/animal) significantly increased the density (Bmax) of thymic glucocorticoid receptors of the adolescent (6 weeks old) and uterine estrogen receptors of adult (10 weeks old) females. The same tendency was observed in the thymus of males and adult females, however without significance. Receptor affinity was (not significantly) influenced in the same direction. Considering that the steroid receptor imprinting effect of vitamins A and D as well as the imprinting-like effect of vitamin E was demonstrated earlier, the ability for neonatal steroid receptor imprinting of the whole lipid-soluble vitamin group is now justified.

Aging↗
PubMed1999

Effect of C2 ceramide on the inositol phospholipid metabolism (uptake of 32P, 3H-serine and 3H-palmitic acid) and apoptosis-related morphological changes in Tetrahymena.

Sphingomyelin metabolites have significant role in the regulation of many life processes of mammalian cells. In the present experiments the influence of phospholipid turnover and apoptosis related morphologic signs by one of this metabolite, C2 ceramide was studied, and compared to the control, untreated cells, in the unicellular Tetrahymena. The incorporation of phospholipid head group components (serine, phosphorus) show a clear time-dependence; while the incorporation of fatty acid component (palmitic acid) is very fast: no significant alterations were found between 5- and 60-min incubations. C2 ceramide treatment didn't alter 3H-palmitic acid incorporation into phospholipids, however 3H-serine incorporation was mainly inhibited. The amount of total incorporated 32P was also decreased, on the other hand the lover concentration C2 ceramide (10 microM) elevated the synthesis of inositol phospholipids. The higher concentration of C2 ceramide (50 microM) had inhibitory effect on the synthesis of each phospholipids examined. This means that in the presence of the C2 ceramide the synthesis, recovery and turnover of phospholipids, participating in signal transduction, are altered. However these observations were based the uptake of labeled phospholipid precursors, which gives information on the dynamics of the process, without using lipid mass measurements. C2 ceramide also caused the rounding off the cells, DNA degradation and nuclear condensation. These latter observations point to morphological signs of apoptosis. The results call attention to the role of sphingomyelin metabolites on signalization of unicellulars, to the cross-talk between the inositol phospholipids and sphingomyelin metabolites, and the role of these molecules in the apoptotic processes at a low evolutionary level.

Animals↗
PubMed1999

The histidine decarboxylase (HDC) gene of Tetrahymena pyriformis is similar to the mammalian one. A study of HDC expression.

RNA was isolated from Tetrahymena pyriformis GL and using human histidine decarboxylase (HDC) gene primers, the RT-PCR product was sequenced. A fraction containing 207 base pairs was compared to the published sequences of prokaryotic and mammalian (rat, mouse and human) HDC cDNA (exons). The HDC-cDNA fraction of Tetrahymena was similar to the mammalian cDNA-s and it was completely different from the prokaryotic HDC-gene. The results indicate the presence of a mammalian-like HDC-gene already in a unicellular eukaryote organism and demonstrates also that the divergence of the prokaryotic-eukaryotic common gene took place already at this low evolutionary level.

Amino Acid Sequence↗
PubMed1999

Fluorimetric analysis of phospholipase activity in Tetrahymena pyriformis GL.

The unicellular Tetrahymena enzymatically split the synthetic phosphodiester, 4-methylumbelliferyl phosphocholine substrate. The enzyme activity was completely blocked in vitro and drastically inhibited in vivo by G-protein activating fluorides (NaF; AIF4- and BeF3-). The phospholipase A2 inhibitor, quinacrine, and the protein phosphatase inhibitor, neomycin, inhibited the enzyme activity in vitro and activated it in vivo. Another phospholipase A2 inhibitor 4-bromo phenacyl bromide was ineffective in vivo and in vitro alike, as well as the cyclooxygenase inhibitor indomethacin. Results of these experiments indicate that some treatments could be specific for a well defined activity (e.g., phospholipase A2, G-protein) but subject to influence by other enzymes (e.g., phospholipase C, sphingomyelinase). The experiments call attention to the differences in the results of the in vivo and in vitro studies.

Acetophenones↗
PubMed1999

The effect of perinatal hormonal imprinting with 13-cis-retinoic acid (isotretinoin) on the thymic glucocorticoid receptors of female and testosterone level of male adult rats.

In earlier experiments, the long-term effect of perinatal treatment (hormonal imprinting) with all-trans-retinol and all-trans-retinoic acid on the thymic glucocorticoid and uterine estrogen receptors was studied and was found effective. In the present experiments, the imprinting effect of four retinoids (13-cis-retinaldehyde, 13-cis-retinoic acid, 9-cis-retinaldehyde and 9-cis-retinoic acid) was investigated, using receptor kinetic analysis and sexual hormone (testosterone and progesterone) level determinations. Exclusively 13-cis-retinoic acid (isotretinoin) had an effect, significantly decreasing glucocorticoid receptor affinity and increasing serum testosterone level. Relationships with RAR-RXR receptor binding and teratogenicity is discussed.

Animals↗
PubMed1999

Effect of vitamin D(3) treatment in the neonatal or adolescent age (hormonal imprinting) on the thymic glucocorticoid receptor of the adult male rat.

Single neonatal treatment with 25 microg vitamin D(3) significantly decreased the thymic glucocorticoid receptor density (B(max)) of 6-week-old male rats. In females, a similar treatment did not cause any changes. Single vitamin D(3) treatment (50 microg) during adolescence (i.e. 6-week-old animals) significantly increased the glucocorticoid receptor density in adult (10-week-old) males. No significant changes in receptor affinity (K(d)) could be observed. Considering that in earlier experiments similar neonatal treatments influenced bone mineral mass and sexual behavior, the hormonal imprinting effect of vitamin D(3) and its harmful effect on the development of other members of the steroid receptor superfamily, seems to be unquestionable.

Aging↗