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Biomedical subjects

G Csaba

Publications and source records attributed to G Csaba.

At least 91 records · Page 5Linked to original sources

Neonatal vitamin E treatment induces long term glucocorticoid receptor changes: an unusual hormonal imprinting effect.

Single neonatal vitamin E treatment significantly altered the affinity (Kd) of thymic glucocorticoid receptors in male adolescent and adult rats. In six weeks old animals the affinity increased (and there is a tendency for an increase in receptor density), in twelve weeks old animals the affinity decreased. The thymic glucocorticoid receptors and uterine estrogen receptors of female animals were not influenced at all. Thousandfold tocopherol did not compete with labeled dexamethasone for their receptors, suggesting that neonatal vitamin E imprinting effect was not done at direct receptorial level.

Animals↗

Imprinting of thymic glucocorticoid receptor and uterine estrogen receptor by a synthetic steroid hormone at different times after birth.

1. Single allylestrenol treatment (hormonal imprinting) of 3-day old rats reduced the density of thymus glucocorticoid receptors and increased the density of uterus estrogen receptors at adult age. 2. Similar treatment of 7-, 14-, or 28-day old animals did not alter the binding capacity of the receptors of the adult animals at all. 3. In 3-day-old animals, the direction of imprinting was similar to the prenatal imprinting of the thymus glucocorticoid receptor (reduction), whereas neonatal treatment of uterine estrogen receptors decreased receptor density, and imprinting on the 4th day increased it. This means that the imprintability persists only to the 4th day; its consequence can be changed. 4. The experiments demonstrate that hormonal imprinting can be provoked by allylestrenol not only pre- or neonatally, as was done in previous experiments, but also a few days later. The imprintability was lost between the 4th and 8th day of life.

Age Factors↗

Fetal digoxin treatment enhances the binding capacity of thymic glucocorticoid receptors in adult female rats.

1. Hormonal imprinting is provoked in the perinatal critical period in the presence of the appropriate hormone or molecules similar to it. As a consequence of hormonal imprinting, the developing receptor finishes its maturation normally (in the presence of the adequate hormone) or abnormally (under the effect of foreign molecules that are able to bind to the receptor). 2. Digoxin--which has a steroid character--caused faulty imprinting by treatments at the 15th, 17th and 20th days of pregnancy. In the adult (3-month-old) animals, the density of thymic glucocorticoid receptors was significantly elevated, whereas the density of uterine estrogen receptors was not, without any change in receptor affinity. 3. The experiments call attention to the steroid receptor imprinting effect of fetal digoxin treatment that must be considered in regard to this treatment at this period and later in regard steroid treatments.

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Effect of fetal digoxin exposure (imprinting) on the sexual behavior of adult rats.

1. Digoxin exposure of rat fetuses at the 15th, 17th and 19th day of pregnancy by treating the mother (with 9 microg digoxin altogether) caused alterations in the sexual behavior of adult rats (3-month-old males and six-month-old ovariectomized and hormone-treated females). 2. The number of active males was significantly higher in the treated group and ejaculation as well as multiple ejaculation occurred only here. Females also were more receptable after fetal digoxin treatment. It is known from the literature that long-term digoxin treatment in adult age influences (reduces) the male sexual activity in humans. In the rat, the opposite effect was observed after fetal treatment. 3. The experiments call attention to the prolonged effect of fetal digoxin exposure caused by the treatment of the mother.

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Effect of neonatal glucocorticoid treatment on bone mineralization of adult nontreated, dexamethasone-treated or vitamin D3-treated rats.

1. Single neonatal dexamethasone (DEX) treatment significantly decreased the body weights of 5-month old male rats. There was no significant difference in females. 2. Bone mineral density (BMD) of neonatally DEX-treated male rats and bone mineral content (BMC) of double DEX-treated (neonatally and in adult age) males were reduced. 3. BMD and BMC calculated to body weight were highly significantly increased after neonatal or double DEX treatment in males. In females only BMC/body weight was elevated after double DEX treatment. 4. Adult vitamin D treatment completely compensated for the changes caused by single or double DEX treatment. 5. The results call attention to the imprinting effects of neonatal glucocorticoid treatment, which were manifested in changes of body weight and bone mineral mass. At the same time the gender-dependence of this phenomenon was demonstrated.

Aging↗

Unspecific binding capacity of androgen receptors in the rat uterus.

Rat uterine cytosol receptor homogenate binds estradiol and testosterone alike. Saturation and displacement studies were done with these two hormones. Testosterone displaced only testosterone while estradiol displaced estradiol as well as testosterone. The experiments call attention to the unspecific binding capacity of rat uterine androgen receptors.

Animals↗

Testosterone and progesterone level alterations in the adult rat after retinoid (retinol or retinoic acid) treatment (imprinting) in neonatal or adolescent age.

Newborn rats were treated with a single dose of vitamin A (retinol), or with three doses of retinoic acid (in the 1st, 3rd and 5th days). Serum testosterone and progesterone level was measured in the four months old male and female rats, respectively. Retinol significantly decreased both hormone levels, however retinoic acid decreased the progesterone level only. In the second part of the experiments adolescent rats (in the 6th and 7th week after birth) were treated and measured similar to the newborns. In this case retinol significantly diminished testosterone level, without influencing the progesterone level. Retinoic acid decreased testosterone level and elevated progesterone level. The results demonstrate the long lasting effects of retinoid treatments at a neonatal or adolescent age, pointing also to the differences in the direction of the effects. Considering that previously the receptorial and sexual-behavioral effects of perinatal vitamin A treatments were observed, the experiments call attention to such harmful influences of perinatal vitamin A treatments, which are not manifested in morphological alterations.

Aging↗

Transgenerational effect of a single neonatal benzpyrene treatment on the glucocorticoid receptor of the rat thymus.

Hormonal imprinting is provoked perinatally by the appropriate hormone on its receptor, causing a life-long adjustment of the connection between the two participants. Faulty imprinting is caused by the presence of molecules similar to the hormone in this critical period, which results in a persistent alteration of the receptor. In the present experiment the transgenerational imprinting effect of a steroid-like environmental pollutant, benzpyrene, on the receptor binding capacity of filial thymic dexamethasone and uterine estrogen receptors was studied. The receptor density (Bmax) of the thymic glucocorticoid receptors of the males was reduced up to the third (F2) generation. In females this reduction was observed only in the F1 generation of treated animals. There was no change in receptor affinity (Kd). Uterine estrogen receptors were not subjected to transgenerational imprinting. The experiments demonstrate (1) the possibility of the transgenerational transmission of imprinting effect, (2) the differences of steroid receptors in different organs, and (3) the differences of male's and female's reactions from this aspect. The results call attention to the dangers of perinatal aromatic hydrocarbon exposition to the progeny generations.

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Effect of single neonatal vitamin D3 treatment (hormonal imprinting) on the bone mineralization of adult non-treated and dexamethasone treated rats.

Hormonal imprinting (the first encounter between the hormone and receptor after birth) is needed for the normal development of receptor. Presence of the appropriate hormone in excess, or its absence, as well as presence of hormone-like molecules able to bind to the maturing receptor in this time, can cause faulty imprinting. In this experiment the effect of neonatal treatment with a single dose of 0.05 mg cholecalciferol (vitamin D3) was studied by bone densitometry. The treatment caused significant decrease of body weight in 3-month old females and also significant reduction of bone mineral density (BMD) and bone mineral content (BMC) in males. Dexamethasone treatment of 3-month old rats for 10 days increased BMD in males and BMC in females without affecting body weight. The double treatment (vitamin D neonatally and dexamethasone when adult) decreased the body weight of both sexes and increased BMD in males, and BMC, BMD/bw and BMC/bw in both sexes, related to the control or the only vitamin D treated groups. Considering the hormonal imprinting effect of neonatal vitamin D treatment at glucocorticoid receptorial level in other experiments, similar effects also can be supposed for vitamin D itself, manifested in the changes of bone mineralization.

Animals↗

Effect of retinoid (vitamin A or retinoic acid) treatment (hormonal imprinting) through breastmilk on the glucocorticoid receptor and estrogen receptor binding capacity of the adult rat offspring.

Hormonal imprinting occurs perinatally when the developing receptor and the appropriate hormone meet each other. The presence of related molecules in this critical period causes misimprinting. Ligands bound to a member of the steroid-thyroid receptor superfamily can disturb the normal maturation of other members of the family, which is manifested in altered binding capacity of the receptor and decreased or increased response of the receptor-bearing cell for life. Excess or absence of the hormone also can cause misimprinting. Treatments once a week for 3 weeks of nursing rat mothers with 6 mg/animal all-trans retinol/dose caused faulty imprinting manifested in significantly reduced density (Bmax) of thymic glucocorticoid receptor in male and female adult progenies alike. 0.03 mg all-trans retinoic acid treatment of nursing mothers was ineffective. Receptor affinity (Kd) was unchanged in both cases as well, as the binding values of uterine estrogen receptors. The results of the experiment call attention to the transmission of imprinter molecules by breastmilk to the progenies, which can cause lifelong alterations at receptorial level and points to the human health aspect. Possible reasons for the differences between retinol and retinoic acid effects and in the sensitivity of receptors are discussed.

Animals↗

The effects of ceramide and its analogues on the secretion of the mucocyst content of Tetrahymena.

Monoclonal antibody to Geodia lectin is bound by the mucocyst content of Tetrahymena. By using this (fluorescent-labelled) antibody and confocal microscopy, the actual state of the mucocyst (position, resting, filling or extruding) can be studied. Treatment with C2 ceramide and non-hydroxy fatty acid caused a rapid depletion of mucocyst material. Another ceramide analogue, psychosine caused fusion of mucocysts. In these cases--in contrast to the controls--the contractile vacuole was filled with mucocyst material and this was seen in the tubules in contact with the contractile vacuoles. Hydroxy fatty acid ceramide, sphingomyelin and sphingosine-1-phosphate were ineffective. As the former materials influence also the cytoskeleton, while the latter do not, the cytoskeleton is presumed to have a mediatory effect. Neither the connection of contractile vacuoles with tubular structures nor mucocyst fusion have been described before.

Animals↗

Phospholipase D activity in the Tetrahymena pyriformis GL.

Phospholipase D (PLD) is an enzyme which participates in the signaling mechanism cleaving phosphatidylcholine (PC) to choline and phosphatidic acid (PA). In Tetrahymena pyriformis GL this enzyme activity is enhanced by different kinds of agonists (sodium orthovanadate, sodium fluoride and phorbol 12-myristate 13-acetate), and its activity can be inhibited by inhibitors such as pertussis toxin, calphostin C, genistein, trifluoperazine. These results suggest that the PLD signalling pathway is connected with the tyrosine kinase, phospholipase C, phosphatidylinositol and G-protein coupled signalling pathways. By demonstrating the PLD activity in Tetrahymena our knowledge on the signaling mechanisms at a unicellular level has been extended. The results support our view that most transducing mechanisms that are characteristic of mammalian cells are also in the protozoan Tetrahymena.

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Identification of lectins in the kinetids of Tetrahymena pyriformis.

Previously we described lectin-like molecules in the ciliate Tetrahymena pyriformis; by application of synthetic neoglycoconjugates it is now shown that T. pyriformis contains considerable amounts of both a beta-D-glucose- and a lactose-specific lectin. No evidence for the presence of alpha-D-mannose-, alpha-D-galactose- or of alpha-L-fucose-specific lectins could be obtained. The two lectins, identified in T. pyriformis, are associated with the kinetids. During cell division the lectins disappear or become masked in the fission furrow. Therefore, we assume that these lectins are involved in the organization of the distribution pattern of the kinetids during cell division perhaps due to lectin-glycoprotein interactions.

Albumins↗

Time- and concentration-dependence of the growth-promoting activity of insulin and histamine in Tetrahymena. Application of the MTT-method for the determination of cell proliferation in a protozoan model.

The unicellular ciliate Tetrahymena pyriformis was treated with different concentrations of insulin or histamine and at different time points the cell density was measured, using a tetrazolium-based semiautomated colorimetric assay (MTT). The assay was suitable to determine the rate of cell proliferation of Tetrahymena. Insulin in each concentration significantly elevated the cell count up to 3 h. After that, it was neutral or its effect was insignificant. Histamine at 10(-5) M concentration diminished cell count at 3, 5, 7 and 24 h. At 10(-6) M concentration there was no difference and at 10(-7) M concentration it enhanced cell division up to 5 h, after that there being no difference. The two hormones have cell division promoting activity for cells of higher animals and the experiments demonstrate this effect already at a unicellular level.

Animals↗

Effects of dipeptides containing the amino acid, proline on the chemotaxis of Tetrahymena pyriformis. Evolutionary conclusions on the formation of hormone receptors and hormones.

Our investigations demonstrate that proline-containing dipeptides can provoke a chemosensory response from the unicellular Tetrahymena pyriformis. The chemotactic effects of the dipeptides have a close relationship with the side chain and the lipophilicity of the amino-terminal amino acid. Comparison of 'mirror' variants of proline-containing dipeptides points to the fact that dipeptides with small side chain and non-polar character amino acids (Gly-Pro, Ala-Pro) are preferred on the amino-terminal end. In the case of amino acids with very variable side chains, small (Pro-Gly) and the large side chain and non-polar character amino acids (Pro-Leu, Pro-Phe) on the carboxyl-terminal end can induce significant chemotactic responses. With valine on any terminus the proline-containing dipeptide induced a weak repellent effect.

Animals↗

Increased apoptosis of adult rat lymphocytes after single neonatal vitamin A treatment (hormonal imprinting). A flow cytometric analysis.

Newborn rats were treated with a single dose of vitamin A (retinol) and apoptosis of peripheral lymphocytes was studied by flow cytometry in adult age. Vitamin A treatment (hormonal imprinting) caused a moderate, however significant elevation in the number of apoptotic lymphocytes after three months. Dexamethasone or Concanavalin-A alone did not influence apoptosis significantly. However, in the neonatally retinol treated rats dexamathasone significantly elevated the quantity of apoptotic lymphocytes related to the control or Concanavalin-A treated control cells. The results call attention to the prolonged effect of hormonal imprinting in a new index and to the possible dangerous effects in human, neonatally treated with vitamin A.

Animals↗

Effect of combined neonatal imprinting by vitamin A, vitamin D3, benzpyrene and allylestrenol on adult rat thymus glucocorticoid and uterine estrogen receptors.

1. Combined neonatal imprinting with allylestrenol, vitamins A and D3 and benzpyrene significantly increased thymic glucocorticoid receptor capacity in male and female animals and decreased receptors affinity in adult females only. 2. Uterine estrogen receptor affinity or density was not influenced. 3. Considering that perinatal treatment with allylestrenol or vitamin D3 decreased glucocorticoid receptor capacity, the dominance of the positive effect of retinol should be surmised. 4. The experiments call attention to the interrelation of different materials acting simultaneously in the perinatal period.

Allylestrenol↗

Effect of 3-amino-1-propanol on the phosphatidylinositol (PI) and glycosyl phosphatidylinositol (GPI) systems of Tetrahymena.

3-Amino-1-propanol (AP), a substance replacing ethanolamine in phosphatidylethanolamine (PE) significantly reduced 32P incorporation to phosphatidylinositol (PI) and glycosyl-phosphatidylinositol (GPI) in the unicellular organism Tetrahymena pyriformis. At 10 mM, AP completely inhibited the incorporation of 32P into PI. 3H-arachidonate incorporation into PI was also inhibited, while that into diacylglycerol (DAG) was high. The experiments indicate the presence and metabolism of inositol phospholipids and GPI in T. pyriformis.

Animals↗