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V Schreiber

Publications and source records attributed to V Schreiber.

At least 55 records · Page 3Linked to original sources
PubMed1996

Triiodothyronine attenuates estradiol-induced increases in dopamine D-2 receptor number in rat anterior pituitary.

Estrogens promote adenohypophyseal enlargement and tumor transformation, and thyroid hormones antagonize these effects. Hormone-induced pituitary enlargement may be mediated by alterations in pituitary dopaminergic function. The present study examined the effects of chronic (20 days) administration of estradiol benzoate (EB), triiodothyronine (T3), or EB and T3 (T3 + EB) on dopamine (D-2) receptors in rat anterior pituitary. D-2 receptor number increased after EB without altered receptor affinity. T3 alone did not affect D-2 receptor number in the anterior pituitary but significantly attenuated the effect of EB. T3 administration also inhibited EB-induced anterior pituitary hyperplasia. D-2 receptor upregulation by EB more likely could reflect a compensatory response to decreased receptor occupation. The present results suggest that D-2 receptors could play an important role in estrogen-induced adenohypophyseal tumor formation and hyperprolactinemia and that thyroid hormones may inhibit estrogen-induced pituitary tumor development via adenohypophyseal D-2 receptors.

Animals↗
PubMed1996

Efficient retroviral infection of mammalian cells is blocked by inhibition of poly(ADP-ribose) polymerase activity.

Integration of proviral DNA into the host cell genome is a characteristic feature of the retroviral life cycle. This process involves coordinate DNA strand break formation and rejoining reactions. The full details of the integration process are not yet fully understood. However, the endonuclease and DNA strand-joining activities of the virus-encoded integrase protein (IN) are thought to act in concert with other, as-yet-unidentified, endogenous nuclear components which are involved in the DNA repair process. The nuclear enzyme poly(ADP-ribose) polymerase (PARP), which is dependent on DNA strand breaks for its activity, is involved in the efficient repair of DNA strand breaks, and maintenance of genomic integrity, in nucleated eukaryotic cells. In the present work, we examine the possible involvement of PARP in the retroviral life cycle and demonstrate that inhibition of PARP activity, by any one of three independent mechanisms, blocks the infection of mammalian cells by recombinant retroviral vectors. This requirement for PARP activity appears to be restricted to processes involved in the integration of provirus into the host cell DNA. PARP inhibition does not affect viral entry into the host cell, reverse transcription of the viral RNA genome, postintegration synthesis of viral gene products, synthesis of the viral RNA genome, or the generation of infective virions. Therefore, efficient retroviral infection of mammalian cells is blocked by inhibition or PARP activity.

3T3 Cells↗
PubMed1996

[Why is it necessary to study the thyroid gland?].

Pathophysiological and clinical aspects of the thyroid gland include after many decades of intensive studies many yet unresolved problems. The relationship with the gastrointestinal system (iodine accumulation in the stomach and salivary glands), the function of thyroxine as a prohormone (in particular the regulation of the activity of tissues deiodinases, the action of triiodothyronine similar to that of steroid hormones, a mixture of protein anabolic and protein catabolic reactions to thyroid hormones, peculiar immune features of the thyroid gland (presence of immunogenic hyperfunctional and hypofunctional syndrome), sharing of common antigens by the thyroid gland and orbital tissues, new findings on mutations of TSH receptors in the thyroid gland, biphasic dependence of the thyroid gland on iodine - all these problems call for further research. Mutation of the TSH receptor can lead to hypothyroidism (resistance to TSH) and to multinodular goitre. The gene for the iodine transporter in the thyroid gland (Na(+)I symport) was cloned. The thyroid gland is related to malignant free radicals: this is suggested also by the raised thyroxine level in rats after methylene blue administration. The increase is recorded in intact as well as carbimazole medicated animals. All this indicates that the thyroid gland must remain in the foreground of research and clinical work: 4% of the Czech population suffer from some thyroid disorder.

Animals↗
PubMed1995

Lasp-1 (MLN 50) defines a new LIM protein subfamily characterized by the association of LIM and SH3 domains.

MLN 50 was previously identified in a cDNA library of breast cancer metastasis. In this study, we show that MLN 50, which is expressed at a basal level in normal tissues, is overexpressed in 8% of human breast carcinomas most often together with c-erbB-2. MLN 50 cDNA encodes a putative protein of 261 residues, named Lasp-1 (LIM and SH3 protein) since it contains a LIM motif and a domain of Src homology region 3 (SH3) at the amino- and the C-terminal parts of the protein, respectively. Thus, Lasp-1 defines a new LIM protein subfamily.

Adaptor Proteins, Signal Transducing↗
PubMed1995

[Endocrinology 1994-1995].

In a brief review of advances made in endocrinology during the past two years surprisingly the receptors for TSH and thyroid hormones occupy the foremost position. Mutations of the TSH receptor may cause congenital hyperthyroidism or resistance to TSH (mutation of the gene for TSH-receptor). An interaction of thyroid hormone receptor with a conserved transcriptional mediator was discovered. The reports on the treatment of neonatal respiratory distress syndrome with TRH are still controversial. CRH deficiency reveals neonatal but not adult glucocorticoid need--at least in mice. The concept of receptors was challenged by the discovery of "inverse agonists", i.e. ligand binding by (already) activated receptors. To make endocrinology even more complicated it was shown, that the congenital lipoid adrenal hyperplasia may be caused not by a deficiency in an adrenal cortex enzyme, but by a mutation of the mitochondrial transport protein (StAR), steroidogenic acute protein). The gene for X-linked congenital adrenal hypoplasia (DAX-1) was isolated, its mutation can cause a hypogonadotropic hypogonadism, too. Animals lacking functional estrogen receptor develop osteoporosis--this is true even in humans. Nitric oxide (NO) has more jobs in the body than previously thought-e.g. for maintenance of diurnal rhythms. The interest in endogenous cannabinoids is still flourishing, especially in the brain. Clinical implications of basic research are best documented by the discoveries of G-protein roles in clinical syndromes (e.g. pseudohypoparathyroidism, McCune-Albright syndrome, acromegaly and "testitoxicosis"). It should be emphasized that Nobel prize for medicine and physiology for the year 1994 was awarded to A. G. Gilman and M. Rodbell for the discovery of G-proteins.

Animals↗
PubMed1995

A dominant-negative mutant of human poly(ADP-ribose) polymerase affects cell recovery, apoptosis, and sister chromatid exchange following DNA damage.

Poly(ADP-ribose) polymerase [PARP; NAD+ ADP-ribosyltransferase; NAD+:poly(adenosine-diphosphate-D-ribosyl)-acceptor ADP-D-ribosyltransferase, EC 2.4.2.30] is a zinc-dependent eukaryotic DNA-binding protein that specifically recognizes DNA strand breaks produced by various genotoxic agents. To study the biological function of this enzyme, we have established stable HeLa cell lines that constitutively produce the 46-kDa DNA-binding domain of human PARP (PARP-DBD), leading to the trans-dominant inhibition of resident PARP activity. As a control, a cell line was constructed, producing a point-mutated version of the DBD, which has no affinity for DNA in vitro. Expression of the PARP-DBD had only a slight effect on undamaged cells but had drastic consequences for cells treated with genotoxic agents. Exposure of cell lines expressing the wild-type (wt) or the mutated PARP-DBD, with low doses of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) resulted in an increase in their doubling time, a G2 + M accumulation, and a marked reduction in cell survival. However, UVC irradiation had no preferential effect on the cell growth or viability of cell lines expressing the PARP-DBD. These PARP-DBD-expressing cells treated with MNNG presented the characteristic nucleosomal DNA ladder, one of the hallmarks of cell death by apoptosis. Moreover, these cells exhibited chromosomal instability as demonstrated by higher frequencies of both spontaneous and MNNG-induced sister chromatid exchanges. Surprisingly, the line producing the mutated DBD had the same behavior as those producing the wt DBD, indicating that the mechanism of action of the dominant-negative mutant involves more than its DNA-binding function. Altogether, these results strongly suggest that PARP is an element of the G2 checkpoint in mammalian cells.

Apoptosis↗
PubMed1995

The effect of an anti-glucocorticoid (ZK 98299) on thymus evolution and on hydrocortisone-induced thymolysis, intestinal brush-border enzymes and their desialylation in suckling rats.

1. The action in Onapristone infant male rats displays short-term and delayed effects. 2. Suppression of intestinal brush-border enzymes and increase of thymus mass were observed only immediately after 3-day treatment with Onapristone. After an additional 3 days its effect disappeared. There was no immediate or delayed effect of Onapristone on the desialylation of brush-border enzymes. 3. In the short-term and delayed effects, Onapristone suppressed the HC-provoked induction of several intestinal brush-border enzymes, especially alpha-glycosidases. In the delayed effect the drug also suppressed thymolysis induced by the exogeneously given glucocorticoid, and suppressed the HC-induced desialylation of a brush-border enzyme DP IV, which serves as a marker of the desialylation process. 4. These experiments seem to support a conclusion that the postnatal development of intestinal brush-border enzymes and the development of thymus in infant rats are controlled by endogeneously secreted glucocorticoids. 5. The control of sialylation of intestinal brush-border proteins by endogeneously secreted glucocorticoids during the postnatal development of the rat remains debatable.

Amylases↗
PubMed1995

Poly(ADP-ribose) polymerase: structure-function relationship.

Dissection of the human poly(ADP-ribose) polymerase (PARP) molecule in terms of its structure-function relationship has proved to be an essential step towards understanding the biological role of poly(ADP-ribosylation) as a cellular response to DNA damage in eukaryotes. Current approaches aimed at elucidating the implication of this multifunctional enzyme in the maintenance of the genomic integrity will be presented.

Animals↗
PubMed1995

Early and delayed effects of hydrocortisone and onapristone on intestinal brush-border enzymes and their sialylation and on thymus growth in suckling rats.

The antigestagen-antiglucocorticoid onapristone (ZK 98.299) was tested on three glucocorticoid-sensitive systems after hydrocortisone (HC) administration to suckling male rats, by determining onapristone (ZK)-induced inhibition of HC-provoked (1) increase of activities of intestinal brush-border enzymes, (2) desialylation of brush-border components and (3) thymolysis. HC acetate (75 mg/kg body weight (b.w.)) was injected s.c. on postnatal days 9 and 10, and ZK (150 mg/kg b.w.) on days 9, 10 and 11. The animals were killed on day 12 for assessing the early effect, or on days 15-17 for determining the delayed effect of HC and ZK. In all three systems the glucocorticoid effects were antagonized by ZK. The most sensitive to HC were systems 1 and 3, which exhibited both the early and the delayed effects. The most sensitive to the counteraction of ZK against administered HC was system 1, where HC was antagonized in both its early and delayed effects, whereas only delayed antagonistic action against administered HC was found in system 2. ZK alone had an early inhibitory effect on the activities of several brush-border enzymes and produced an early increase in thymus weight, accompanied by an increased DNA-protein ratio. No delayed effects of ZK alone on the three systems were observed.

Animals↗
PubMed1995

An increase in the blood thyroxine level after methylene blue in rats: the interaction with carbimazole.

Anterior pituitary (AP) weight, thyroid weight, the serum thyroxine (T4) level, the thyroid T4 and cAMP content, the serum TSH level and the TSH and cAMP content of the AP and thyroid were measured in control rats, rats given methylene blue (MB) in their food, rats given the thyroid-blocking agent carbimazole (CARB) and rats fed both MB and CARB. AP weight fell slightly after MB in both intact and CARB--fed animals. Thyroid weight rose strongly after CARB, MB partly inhibited this increase. The cAMP content of the thyroid rose after CARB; this increase was likewise blocked by MB, MB alone had no effect on the thyroid cAMP concentration. Previous observations showing that MB produced an increase in the blood T, were confirmed. The T4 level fell, of course, after CARB and the decrease was partly inhibited by MB. The T4 content of the thyroid also fell after CARB, this decrease was completely reversed by MB. The blood TSH level fell slightly after MB and rose 7--fold after a CARB blockade of the thyroid; this increase was completely inhibited by MB. The TSH content of the AP fell after MB in both intact and CARB--fed animals. The cAMP content of the AP fell after MB, it was unaffected by CARB. Thus, in some way, MB raised the blood thyroxine level in both intact and CARB--fed animals and strongly depressed the TSH content in the serum and the AP given alone or with CARB. The mechanism of this action should be a result of MB interaction in thyroid hormone metabolism and their binding activity on specific regulatory elements. It is a problem for future experiments.

Administration, Oral↗
PubMed1995

[Methylene blue as an endocrine modulator: interactions with thyroid hormones].

Methylene blue (MB) is a thiazine dye used in the treatment of methemoglobinemia. Since it was shown to scavenge free radicals, it is now being examined clinically in reperfusion syndrome and septic shock. We tested methylene blue in a series of experimental endocrine situations, in which this scavenging effect could play a role. Indeed, we observed that MB partly inhibited the increase in adenohypophyseal weight and cAMP and prolactin levels after the administration of estrogens in male rats. MB also inhibited the increase of another scavenger of free radicals, the metalloenzyme ceruloplasmin in the blood of estrogenized rats. MB also inhibited the stimulation of bone mass after estradiol in male rats. In this respect, it behaved as an antiestrogen. In the bones, MB also prevented the increase of bone minerals induced by estradiol. MB also produced a decrease in adenohypophyseal ascorbic acid content an potentiated the effect of estradiol in the same direction. Surprisingly, blood thyroxine levels increased consistently in rats after MB treatment. An interaction of MB with thyroid hormone synthesis and/or actions thus should be evaluated. This idea is supported by our observation of an antagonistic action of MB in carbimazole-induced rise in thyroid weight and decrease in thyroxine blood levels. (Ref. 14.).

Animals↗
PubMed1995

Anabolic effects of progestogens in bone remodelling.

The short-term effects of oestrogen deficiency on biochemical indices of bone turnover were studied in 49 women who had undergone hysterectomy with bilateral ovariectomy. In patients treated with norethisterone or tibolone, a significant reduction was observed in urinary hydroxyproline excretion comparable to that observed in estradiol treated patients. Bone isoenzyme of serum alkaline phosphatase activity did not decrease and bone mass remained increased during norethisterone and tibolone treatments. It is concluded that norethisterone and tibolone can act as bone-trophic hormones.

Alkaline Phosphatase↗
PubMed1995

Methylene blue--an endocrine modulator.

Methylene blue (MB) is a thiazine dye used in the treatment of methemoglobinemia. It may represent a new class of anti-oxidant drugs which competitively inhibit the reduction of molecular oxygen to superoxide by acting as an alternative electron acceptor for tissue oxidases. Because of its strong free radicals scavenging effect MB was experimentally used in the treatment of reperfusion syndrome. MB is soluble guanylate cyclase inhibitor. It was found to inhibit the stimulation of soluble guanylate cyclase by nitric oxide and vasodilatators. Another effect of MB is inhibition of prostacyclin synthesis by endothelial cells and isolated arteries independently of its effects on cGMP accumulation. We investigated the MB in series of experimental endocrine situations in which its free radicals scavenging effect could play a role. We observed that MB partly inhibited the increase in adenohypophyseal weight, cAMP and blood prolactin levels in male rats after the administration of estrogens. MB also blocked the increase of another free radicals scavenger-the metalloenzyme ceruloplasmin in the blood of estrogenized rats and prevented the increase of bone mineral after estradiol treatment. MB produced a decrease in adenohypophyseal ascorbic acid content. The blood thyroxine levels increased and the anterior pituitary TSH concentration decreased after MB treatment.

Animals↗
PubMed1995

[Experimental neuroendocrinology].

A short review of the history of experimental neuroendocrinology is given. The influence of light on the endocrine system, hypothalamic regulation of the adenohypophysis and neurosecretion are discussed. At the IIIrd Medical Dept.-under influence of professor Charvát-I first studied the influence of light (following the findings of Rowan, Scharrer, Benoit and others). After the Harris' discovery that the hypophysial portal system serves for transport of hypothalamic hypophysiotropic factors I relatively early (1949) started to study the hypothalamic extracts, aiming to demonstrate the existence of these factors, the regulating hormones (RH) of today. Our successful attempt to demonstrate TRH (1961) as well the unsuccessful attempt do achieve its chemical constitution are described. Thereafter we studied the mechanisms of adenohypophyseal growth: estrogen-induced adenohypophyseal hypertrophy is inhibited by testosterone, thyroxine and dopaminergic agonists, it is potentiated by dopaminergic antagonists. An inhibitory action is displayed also by methylene blue. There is a correlation between the blood ceruloplasmin (polyphenoloxidase) level and growth of the adenohypophysis after estrogens: methylene blue inhibits both reactions. Finally, we codiscovered the endogenous digitalis-like activity and first demonstrated its origin in the adrenals; we also obtained the preliminary evidence for the existence of quinidine-like endogenous factor.

Animals↗
PubMed1995

Three autacoids--endogenous digitalis-like factor, clonidine-displacing substance, and quinidine-like immunoreactivity.

The existence of endogenous ligands of opioid receptors prompted research of a potential endogenous digitalis-like factor (DLF) and of endogenous clonidine-displacing substance (CDS). Within eleven years of research, endogenous ouabaine was identified as DLF. It originates in the adrenal cortex. Its physiological role is not yet clear. Most probably, endogenous ouabaine is primarily active in regulation of natriuresis and of blood pressure. The CDS originates in the brain and is active in regulation of blood pressure as well. Its chemical formula was recently identified as agmatine. The potential presence of further autacoids like, e.g. endogenous quinidine-like substance remains to be clarified.

Animals↗
PubMed1995

[Acute phase proteins].

Various plasma protein patterns following inflammation and metabolic stress were described since diagnostic value of ESR was established. This reactive dysproteinemia is now recognized to reflect the shift in hepatic proteosynthesis after the immunoendocrinological activation. Four main groups of mediators are necessary for expression of hepatic positive and negative acute phase proteins (APPs): first and second "wave' of proinflammatory cytokines, further glucocorticoids and growth factors including insulin. Actual data showing details of the immunological and endocrinological regulation of stress hepatocyte proteosynthesis are summarized and our own results are presented. We evaluated the diagnostic use of APPs in some defined clinical situations (neutropenic period after bone marrow transplantation, postoperative complications) and correlated APPs with the plasma levels of the circulating interleukin-6 and cortisol. In another study, APPs, plasma and urinary TNF, interleukin-6, interleukin-8 and adhesive molecules ICAM-1, VCAM-1 were found to be significantly different in various glomerulopathies. Finally, our experimental data indicate the nitric oxide participation in oestradiol regulation of coeruloplasmin synthesis in rat.

Acute-Phase Proteins↗
PubMed1995

Image analysis of argyrophil nucleolar organizer regions (AgNORs) in oestrogen-induced rat anterior pituitary hyperplasia: comparison of automatized (LUCIA M) and non-automatized evaluation.

Argyrophil nucleolar organizer regions (AgNORs) were morphometrically evaluated in rat anterior pituitaries of control and oestrogenized rats using an automatized (LUCIA M--Laboratory Universal Computer Image Analysis Micro) and a non-automatized approaches to investigate not only the sensitivity and effectiveness of the automatized procedure but also the morphology of AgNORs in oestrogen-induced rat anterior pituitary hyperplasia. In the experimental oestrogen-induced rat anterior pituitary hyperplasia, the image analysis system LUCIA M was compared to a non-automatized morphometric procedure and proved to be very efficient and yielded analogical results. The AgNOR morphology in the oestrogenized pituitaries was characterized by an increase of the total AgNOR area and clustering of AgNORs in the large nucleoli.

Animals↗