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Biomedical subjects

C Karabélyos

Publications and source records attributed to C Karabélyos.

At least 19 recordsLinked to original sources

The effect of a single neonatal treatment (hormonal imprinting) with the antihormones, tamoxifen and mifepristone on the sexual behavior of adult rats.

Hormonal imprinting takes place perinatally during the first encounter between the hormone and its developing receptor. The presence of an excess of related molecules in that time provokes faulty (pathological) imprinting. In the present experiments single-neonatal treatment with 100 microg of tamoxifen completely abolished the adult male and female rats' sexual activity. Similar treatment with 100 microg of mifepristone (RU486) significantly enhanced the males sexual activity and non-significantly increased that of the females. The results demonstrate the importance of pathological imprinting during the perinatal development of sexual behavior. There are clear differences between the molecules having steroid (mifepristone) or non-steroid (tamoxifen) character, mediated through a ligand-receptor complex, and its effect in activating particular genes.

Animals↗

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↗

[Refsum disease].

For the first time in literature the authors interpret the pathography of Refsum's disease, in the case of their patient, as pseudo-hypervitaminosis A. The biochemical basis of the clinical picture is a defect in the activity of phytanic-acid-alpha-hydrolase belonging to the peroxisomal system. As a consequence, phytanic acid accumulates in the serum and in the parenchymal tissues. Retinol, an alcohol with high molecular weight, is a natural ligand of nuclear RXR (retinoid-X-receptor), which plays an important role in the regulation of peroxisoma synthesis. In Refsum's disease the phytanic acid accumulated because of the enzyme defect competes with the biotransformation derivates (all-trans-retinoic acid, 9-cis-retinoic acid) of the all-trans-retinol (vitamin A) for the nuclear RX receptor binding sites, and as a very potent receptoractivator it causes the intestinal symptoms of hypervitaminosis A. The authors review the procedure of fatty-acid chromatography necessary for the establishment of the diagnosis and discuss--in addition to dietary restrictions--recent therapeutic possibilities, like plasmapheresis, cascade filtration, lipapheresis and oral batylalcohol treatment.

Child, Preschool↗

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↗

Elevated hepatic glucocorticoid receptor expression during liver regeneration in rats.

In rats within the first week of partial hepatectomy reconstruction of the normal histological structure of the liver already starts. To approach the possible role of endogenous glucocorticoids in the process of regeneration we measured the changes in the expression of steroid glucocorticoid receptor gene after various regeneration intervals. After partial hepatectomy, between 0.5 168 hours from the surgery, the gene expression (mRNA) of glucocorticoid receptor was determined by reverse transcription followed by PCR and normalized to that of glycerolphoshate dehydrogenase. Two peaks of glucocorticoid receptor mRNA were detected first, between 3 and 6 hours (first peak) and a second between 24 and 36 hours. Immunoreactive glucocorticoid receptor was detected by immunohistochemistry using monoclonal anti-glucocorticoid receptor. Three days after the surgery immunohistochemical studies showed substantially more immunoreactive GcR protein in the regenerated liver than in the controls. These semiquantitative data provide evidence suggesting elevation of glucocorticoid receptor expression during regeneration of liver at mRNA and protein levels.

Animals↗

Investigation on the formation of the hormone reception mechanism.

The formation of the hormone receptor mechanism is part of the embryonic development. The perinatal age seems to be critical for the maturation of this system, i.e. the development of the proper hormone selectivity, the number of the receptors, their sensitivity to the adequate hormone. Our team tried to get a closer view on this developmental period examining different parameters in different model systems. We were able to show that during the maturation of the hormonal system similar responses could be elicited by the later specific hormones or by the non-specific ones but structurally similar compounds. Also it became evident that one single hormonal treatment, applied during in the perinatal age, could influence the responsiveness to hormones of the adult animals.

Embryo, Mammalian↗

Effect of digoxin imprinting in adolescence on the sexual behavior of adult rats.

Four-time 3 micrograms digoxin treatment of male rats at puberty (in six weeks old rats) significantly increased the libido of rats (number of intromissions) and reduced the number of ejaculations, two months after the treatments (in three and a half months old rats). In female rats the Meyerson index and lordosis quotient were not significantly decreased. The experiment calls attention to the wide-ranging imprinting effect of digoxin which was also demonstrated earlier after prenatal (maternal) treatment. The experiment also supports the male sexual potency influencing effect of digoxin treatment, previously supposed in men.

Aging↗

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.

Animals↗

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↗

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↗

Transgenerational effect of a single neonatal benzpyrene treatment (imprinting) on the sexual behavior of adult female rats.

Male and female rats were neonatally treated with a single dose of benzpyrene. The adult animals were mated inter se, forming control-control, benzpyrene (female)-control, benzpyrene (male)-control, and benzpyrene-benzpyrene treated couples. In the F1 and F2 generations (without any further treatment) the females's sexual behavior was tested to Meyerson index and lordosis quotient after ovariectomy and hormone treatment, using experienced males. In the F1 generation both indices were significantly reduced in the maternally treated, paternally untreated groups, however this reduction was not present in the group where the treatment was maternal and paternal alike. In the F2 generation, beside the more expressed reduction in the grandmaternally treated group, a moderate reduction in the sexual activity of progenies having treated grandfather or two treated grandparents were observed. The experiment call attention to the transgenerational sexual behavioral effect of a dangerous environment pollutant, benzpyrene.

Animals↗

Contraceptive treatment increases the affinity of uterine estrogen receptor in adult rat: perinatal gestagen treatment changes the reaction.

Uterus estrogen receptor affinity increases in adult rats if treated with contraceptive, without receptor density change. Uterus estrogen receptor density decreases in adulthood following allylestrenol (Gestanon) treatment perinatally with receptor affinity unchanging. In perinatally allylestrenol treated rats contraceptive treatment resulted in the decrease of receptor affinity and increase of density, related to the only perinatally allylestrenol treated animals. The results draw attention to the fact that contraceptives may influence the estrogen receptor state of the uterus and the pregnancy maintaining treatment (by allylestrenol) may influence the state of uterine estrogen receptors for life via the later effect of contraceptives commonly dosed.

Allylestrenol↗

Changes in sexual behavior of adult male and female rats neonatally treated with vitamin D3.

1. Neonatal treatment of rats with vitamin D3 resulted in a change of sexual behavior in adulthood. 2. 2.5 mg vitamin D3 completely inhibited the ejaculation of males without any apparent influence on sexual desire. 250 mg vitamin D3 influenced both the desire and ejaculation. 3. Sexual activity of females was depressed by both doses. 4. The experiments demonstrate that vitamin D3, a steroid in structure, given in the critical period of hormonal imprinting may influence steroid hormone-receptor commanded events for life, in a way similar to the effects exhibited by synthetic steroid hormone analogues and benzpyrene in earlier studies.

Analysis of Variance↗

Effect of neonatal treatment with monoclonal antibody to thyrotropin (TSH) receptor on the thyroxin (T4) level and certain parameters of the internal genital organs of adult rats.

Treatment of newborn rats with a single dose of monoclonal antibody to TSH receptor, caused permanent changes in the body weight, T4 level, and different sexual parameters. There are considerable sex and organ dependent differences in the sensitivity. Body weight and physical condition of males deteriorates, while the condition of the females is constant. However, T4 level of females significantly increases while that of the males does not change. The weight of seminal vesicle increases, while ovarian weight decreases. Effect of hCG treatment in adult age is inhibited by neonatal antibody (to TSH receptor) treatment. The experiment calls the attention to the imprinter effect of antibodies in the neonatal critical period, which effect could be manifested on the antibody's own (provoked) or foreign (related) receptor.

Animals↗

Benzpyrene treatment decreases the sexual activity of adult rats, what is reversed in neonatally allylestrenol treated animals.

In neonatally allylestrenol treated animals in adult age a single benzpyrene treatment significantly decreases the female and significantly increases the male rat's sexual activity. Three month old females display the negative sexual behavioral effect of neonatal allylestrenol treatment less than the six month old ones. The benzpyrene treatment in adult age decreases the sexual activity of male rats. The experiments call the attention to the modifying effect of perinatal steroid treatments to similar exposure in adult age.

Aging↗

Hormonal imprinting: neonatal treatment of rats with the peroxysome proliferator clofibrate irreversibly affects sexual behaviour.

In the rat, the peroxysome proliferator activated receptor (PPAR) inducer clofibrate can moderately influence the hormone (testosterone) level and, after single perinatal treatment, irreversibly affects sexual behavior through the mechanism of hormonal imprinting. The thymic glucocorticoid and estrogen receptors weren't significantly influenced. The experiments call the attention to the universality of false imprinting by molecules able to bind to the steroid/thyroid receptor superfamily, and point to the different sensitivity to different ligands.

Animals↗

Effect of nifedipine treatment (imprinting) of rat feti and newborns on the responsiveness of adult rat's uterus. Extension of the imprinting theory.

1. The uterus of adult progeny of rats treated with nifedipine during the late phase of pregnancy react in vitro to oxytocin less and the contractility of ones treated with higher dose (100 micrograms) disappears. 2. There is a more pronounced deficiency or lack of responsiveness in five week old animals treated with nifedipine neonatally. 3. The experiments demonstrate that perinatal imprinting can be developed not only on hormone receptors and enzymes but on ion (Ca2+) channels of the plasma membrane. Consideration of this fact might have an importance in clinical aspects too.

Animals↗

Pubertal benzpyrene exposition decreases durably the sexual activity of the adult male and female rats.

Single benzpyrene treatment of 5 week old male and female rats significantly decreased their sexual activity at 3 months of age. Among the hormone preparations used nandrolone was comparatively practically ineffective, while estradiol decreased the lordosis quotient of females. In males benzpyrene produced a total failure of ejaculation. These results draw attention to the wide time-scale of receptorine and behavioral effects of the aromatic hydrocarbon, benzpyrene. These effects are detectable following fetal, neonatal or pubertal treatments, especially in females. In males, the negative effect was manifested after neonatal and pubertal treatments only. The experiments suggest that in some cases hormonal imprinting does not develop solely in the perinatal period but it might develop later.

Anabolic Agents↗