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At least 433 records · Page 24Linked to original sources

[Interaction of blood sex steroid-binding globulin-steroid complexes with plasma membranes of human decidual endometrium cells].

Plasma membranes of decidual tissue cells specifically bind the sex steroid-binding globulin (SBP) complexes with estrogen (estradiol, estriol, estrone) and with the pharmacological agent danazol but do not interact with the SBP-testosterone or SBP-dihydrotestosterone complexes. The selectivity of interaction of the SBP-steroid complexes with decidual tissue cellular membranes provide evidence for the active role of SBP in the realization of steroid effects on the target tissue.

Cell Membrane↗

[Phylogenesis of steroid-transport proteins in the blood: detection and characteristics of the sex-steroid-binding protein in the blood plasma of the carp].

The interaction of 3H-5 alpha-dihydrotestosterone, 3H-progesterone, 3H-cortisol and 3H-testosterone with the Cyprinus carpio blood proteins was studied by means of adsorption on the activated charcoal and equilibrium dialysis. Protein which specifically binds androgen-, estradiol-, progesterone- and, to a lesser degree, corticosteroids was present in the blood plasma. The equilibrium constants of 3H-steroid association with this protein, the concentration off steroid-binding sites and its hormonal specificity of the affinity were determined. There were no pronounced sex dimorphism and marked alterations in the concentration of protein-binding sites during ontogeny and reproduction process. Protein, being specialized on the corticosteroid transport, was not revealed in the Cyprinus carpio blood plasma. It is suggested that the formation of differentiated corticosteroid-binding globulin and sex steroid-binding protein, typical of higher vertebrates, occurred during the stage of teleostei.

Androgen-Binding Protein↗

[An immunopathological study during steroid-responsive and steroid-nonresponsive stages on a patient with neuro-Behçet's disease].

We followed up the clinical course and changes of brain magnetic resonance imaging (MRI) findings in a case of neuro-Behçet's disease, and performed serial immunological examinations of the cerebrospinal fluid (CSF). On the two episodes of acute exacerbation, gadolinium (Gd)-enhancement effects on brain MRIs were observed in the brain stem and the deep white matter of cerebral hemispheres. The CSF abnormality of this period was characterized by increases in proportions of polymorphonuclear leukocytes and intrathecal IgG synthesis in addition to the findings suggesting breakdown of the blood brain barrier (BBB). These findings disappeared in parallel with clinical improvement by corticosteroid therapy. In contrast, during a subsequent chronic progressive stage, steroid-resistant neuropsychiatric symptoms and an absence of Gd-enhancement effects on brain MRIs were observed despite progressive breakdown of BBB. These findings suggest that neuro-Behçet's disease should comprise two distinct immunopathogenetic stages, that is, a relatively early steroid-responsive stage with a relapsing-remitting clinical course and a late steroid-nonresponsive stage with a chronic progressive course.

Behcet Syndrome↗

Testis cytological structure, plasma sex steroids, and gonad cytosol free steroid receptors of heterologous gonadotropin (hCG)-stimulated silver eel, Anguilla anguilla L.

Complete testicular maturation was induced in silver eels, kept at 24 degrees in fresh water, by a single injection of 1000 I.U. of heterologous gonadotropin (hCG). Each week, for 4 weeks, some eels were examined for testis structural pattern, plasma sex steroids, and gonad cytosol steroid receptors. The first effect of the hCG was on the tubular organization of the testis, followed by spermatogenesis. Plasma androgens were not detectable in the untreated eels, whereas a peak was detected a week after in those treated with the injection and afterward a decline. Plasma progesterone and estradiol showed a peak 2 weeks after treatment. Untreated eel gonads showed a high content of cytosolic free estradiol receptors which disappeared in the hCG-treated ones, a peak of free progesterone receptors was found 1 week after injection. The results are discussed in relation to the differentiation and maturation of eels testes.

Anguilla↗

Microbial transformations of steroids--X. Cytochromes P-450 11 alpha-hydroxylase and C17-C20 lyase and a 1-ene dehydrogenase transform steroids in Nectria haematococca.

Nectria haematococca contains four enzymes that metabolise exogenous steroids. Two of these are microsomal cytochromes P-450 which act sequentially on progesterone producing firstly, by side-chain cleavage, the C19 steroid androstenedione (C17-C20 lyase), and then, in a subsequent set of transformations, 11 alpha-hydroxylated derivatives (11 alpha-hydroxylase). Two other conversions occur after side-chain cleavage. Unsaturation, in the form of a double bond at C1-C2, is introduced into the A ring by a catalytically self-sufficient microsomal 1-ene dehydrogenase. This enzyme is specific for C19 substrates. A C17-specific oxidoreductase is also involved in the production of androstenedione and testosterone from progesterone. The lyase, 11 alpha-hydroxylase and 1-ene dehydrogenase were purified to homogeneity.

Androstenedione↗

The mitochondrion as a primary site of action of steroid and thyroid hormones: presence and action of steroid and thyroid hormone receptors in mitochondria of animal cells.

Mitochondria are key cellular organelles that regulate events related to energy production and apoptosis. These processes are modulated, in turn, by steroid and thyroid hormones in the course of their actions on metabolism, growth and development. In this context, a direct effect of these hormones on the mitochondrial-linked processes, possibly by way of cognate mitochondrial receptors, has been proposed. In this paper we review data from the literature and present new findings supporting this concept. Receptors for steroid hormones, glucocorticoids and estrogens, and for T(3), have been detected in mitochondria by immunofluorescence labeling and confocal laser microscopy, by Western blotting of mitochondrial proteins and by immunogold electron microscopy. Furthermore, the mitochondrial genome contains nucleotide sequences with high similarity to known hormone-responsive elements, which interact with the appropriate receptors to confer hormone-dependent activation of reporter genes in transfection experiments. Thus, thyroid hormone stimulates mitochondrial transcription mediated by the cognate receptor when added to an in organello mitochondrial system, capable of faithful transcription.

Animals↗

Steroid hormones. Membrane transporters of steroid hormones.

The discovery of a plasma membrane ABC protein that exports steroids in yeast highlights the possibility that similar membrane sorting systems in mammalian cells may modulate the access of steroids to their receptors.

ATP-Binding Cassette Transporters↗

CREB binding protein acts synergistically with steroid receptor coactivator-1 to enhance steroid receptor-dependent transcription.

Steroid receptors are ligand-regulated transcription factors that require coactivators for efficient activation of target gene expression. The binding protein of cAMP response element binding protein (CBP) appears to be a promiscuous coactivator for an increasing number of transcription factors and the ability of CBP to modulate estrogen receptor (ER)- and progesterone receptor (PR)-dependent transcription was therefore examined. Ectopic expression of CBP or the related coactivator, p300, enhanced ER transcriptional activity by up to 10-fold in a receptor- and DNA-dependent manner. Consistent with this, the 12S E1A adenoviral protein, which binds to and inactivates CBP, inhibited ER transcriptional activity, and exogenous CBP was able to partially overcome this effect. Furthermore, CBP was able to partially reverse the ability of active ER to squelch PR-dependent transcription, indicating that CBP is a common coactivator for both receptors and that CBP is limiting within these cells. To date, the only other coactivator able to significantly stimulate receptor-dependent transcription is steroid receptor coactivator-1 (SRC-1). Coexpression of CBP and SRC-1 stimulated ER and PR transcriptional activity in a synergistic manner and indicated that these two coactivators are not functional homologues. Taken together, these data suggest that both CBP and SRC-1 may function in a common pathway to efficiently activate target gene expression.

CREB-Binding Protein↗

[Effects of various steroidal and non-steroidal anti-inflammatory drugs on in-vitro IL-10 production of murine peritoneal macrophages infected with Mycobacterium avium complex].

In murine infections due to Mycobacterium avium complex (MAC), bacterial regrowth of the pathogens is frequently encountered in the relatively late phase of infection even in mice receiving daily treatments with antimicrobial agents including rifamycins and macrolides. In this case, the bacterial regrowth is usually accompanied by concomitant increase in the tissue levels of IL-10 and transforming growth factor-beta (TGF-beta), well known immunosuppressive cytokines. In this context, it is of interest to note recent findings that steroidal anti-inflammatory drugs up-regulate TGF-beta production from T lymphocytes, thereby suggesting participation of immunosuppressive cytokines in the expression of their anti-inflammatory activity. In this study, we examined the effects of various anti-inflammatory drugs including glucocorticoids and non-steroidal anti-inflammatory drugs (NSAID) on in-vitro IL-10 production of murine peritoneal macrophages (M phi s) infected with MAC organisms. When the IL-10 production by MAC-infected M phi s was measured in terms of protein and mRNA expression of the cytokine using ELISA and RT-PCR assays, the following results were obtained. First, the IL-10 production into M phi culture fluids was temporarily increased around days 1 to 3, thereafter gradually declined, and returned to normal by day 14. Secondly, IL-10 mRNA expression of M phi s was rapidly induced after MAC-infection and the maximum level of the mRNA expression was achieved at 2 hr. Thereafter, IL-10 mRNA expression ceased rapidly and returned to normal by 24 hr. Thirdly, the majority of test anti-inflammatory drugs, not only glucocorticoids but also NSAID, were found to up-regulate the IL-10 production of MAC-infected M phi s, suggesting some possible roles of IL-10 in the expression of the anti-inflammatory activities of these agents.

Animals↗

HET-CAM bioassay as in vitro alternative to the croton oil test for investigating steroidal and non-steroidal compounds.

In this study the irritation phenomena at the chorioallantoic membrane of incubated hen's eggs as an in vitro model (HET-CAM assay) were investigated in comparison to the in vivo croton oil test by including hydrocortisone, indomethacin, phenylbutazone, acetylsalicylic acid, rutin, quercetin, apigenin, and p-coumaric acid as steroidal and non-steroidal test substances. For the first time the two methods were compared in a valid way with the perspective of a realistic reduction of animal experiments. It should be investigated whether an in vitro-in vivo correlation exists and, if there is any possibility, to replace the in vivo model by an in vitro test system. Both bioassays were able to demonstrate the anti-inflammatory potency of the constituents tested. The determination of the anti-inflammatory activity of all compounds in the two test systems showed individual trends of inhibitory effects. However, the in vitro HET-CAM test was much more sensitive in comparison to the in vivo croton oil test. The croton oil test gave dose-effect correlations in the anti-inflammatory substances investigated. The modified HET-CAM assay did not provide clear dose-effect ratios. The HET-CAM assay is an inexpensive test being easy to manage after a short practical training. Because of its sensitivity the HET-CAM assay could be considered a suitable tool for qualitative testing of the anti-inflammatory activity of substances if no appropriate dose-effect curves are required. From these results it can be concluded that the different courses of the dose-effect curves may be primarily due to different mechanisms of action.

Allantois↗

Hormone and immune response, with special reference to steroid hormone. 2. Sex steroid receptors in rat thymus.

In this study, we characterized the sex hormone receptors in normal and abnormal rat thymus tissues using biochemical and immunohistochemical techniques. Judging from the experimental results, the progestin and the estrogen receptor-containing cells and the thymulin-producing cells are the same reticuloepithelial (RE) cells. This suggests that the sex steroids mediate immune functions of the thymus through receptors within the RE cells to produce thymulin which induces the thymocyte to differentiate and mature. Whether the sex hormones have any direct effects on either T or B cells is not known at this time. So, further studies are needed to clarify this point. Secondly, using the spontaneously developed thymoma tissues from BUF/Mna rat the present authors have just started to biochemically analyse the existence of sex hormone receptors and to immuno-histochemically identify sex hormone receptor-containing cells and thymulin-producing cells. As a contemporary result, progesterone and estrogen receptors were mainly located in the intact RE cells but not in the neoplastic cells, whereas thymulin-producing cells were in both intact RE cells and neoplastic cells. It seems by now that there is no correlation between steroid hormone receptors and thymulin production in the neoplastic cells, as would be in the intact RE cells. Further study is required to answer this question.

Animals↗

The role of a peripheral dopamine-antagonist (Motilium) in improving the tolerance to steroidal and non-steroidal anti-inflammatory agents.

Domperidone protective therapy has been applied in 50 patients suffering from locomotor disease, who responded with dyspeptic complaints to the steroidal and non-steroidal antiphlogistic therapies which meant a risk of the activation of an earlier gastro-intestinal disease. The basic therapy could be applied to 80% of patients due to the Motilium protection because of the favourable changes in gastro-intestinal symptoms. Since domperidone is well tolerated by the patients and it does not yield higher risks, it's use is highly recommended as a protective therapy as well.

Anti-Inflammatory Agents↗

Effect of some steroidal & non-steroidal anti-inflammatory drugs on purified goat brain cathepsin L.

The lysosomal cysteine proteinases have been found to be involved in various inflammatory conditions. Inhibitory effects of certain commonly used anti-inflammatory drugs were observed on lysosomal thiol proteinase cathepsin L. Of the non-steroidal anti-inflammatory drugs tested, phenylbutazone was found to be most potent inhibitor of cathepsin L activity. The half maximal inhibition was achieved at 0.6 mM concentration. The inhibition by phenylbutazone was of non-competitive type, with a ki of 1.3 x 10(-3) M. Flufenamic acid and indomethacin were also inhibitory to cathepsin L activity, giving half maximal inhibitions at 3.5 mM and 4.5 mM concentrations respectively. In contrast, cathepsin L activity was not affected at all by steroidal anti-inflammatory agents. Aspirin was also found to have no effect on cathepsin L activity whereas salicylic acid, its m- and p-analogs exhibited inhibitory effects but to a lesser degree.

Animals↗

[Interrelationship of microsomal and mitochondrial systems for hydroxylating steroids from cattle adrenal cortex: effect of highly-purified components of the mitochondrial monoxygenase system on hydroxylation of steroids by microsomes].

The possibility of functioning of microsomal steroid hydroxylases in the adrenal cortex in the presence of the electron-transporting proteins in mitochondrial monooxygenase systems has been studied. It was found that adrenodoxin reductase stimulates both the 21- and 17 alpha-steroid hydroxylation activities in microsomes of the adrenal cortex with the same efficiency as does NADPH-dependent cytochrome P-450 reductase. Using cytochrome b5 and its specific antibody, an attempt has been made to investigate possible mechanisms of the stimulating effect of adrenodoxin reductase.

Adrenal Glands↗

Intrauterine position effects on steroid metabolism and steroid receptors of reproductive organs in male mice.

Mice differ in their adult reproductive characteristics as a function of whether they developed in utero between two male fetuses (2M males), which have higher testosterone levels, or between two female fetuses (0M males), which have higher estradiol levels. The present study was designed to further characterize biochemical parameters of 2M and 0M adult male mice. Activities of testicular steroidogenic enzymes, namely delta 5-3 beta-hydroxysteroid dehydrogenase/isomerase, 17 alpha-hydroxylase, and C17,20-lyase (C21SCC P450), were measured by means of radiometric assays and HPLC fractionation of substrate and products. Activity of 5 alpha-reductase in both seminal vesicle and prostate was measured by similar techniques. Estrogen and androgen receptor concentrations, which indicate capacity to respond to steroid hormones, were also examined in the accessory sex organs. For both seminal vesicle and prostate, 5 alpha-reductase activities were approximately 60% greater in 2M males than in 0M males, indicating greater capacity to form dihydrotestosterone from testosterone in organs from 2M mice. No significant differences were found in testicular steroidogenic enzymes between 2M and 0M animals, whereas the trend for all three activities was higher for 2M males than for 0M males. While no differences were found in estrogen receptor concentrations, 0M prostates had three times the concentration of androgen receptors (occupied receptors) compared to 2M prostates. Our findings suggest that intrauterine fetal position exerts a significant influence on subsequent adult androgen metabolism and androgen responsiveness in reproductive organs of adult male mice.

Aldehyde-Lyases↗

Steroidal derivatives. Part 4: Synthesis and in vitro anabolic and catabolic properties of a new group of steroidal alkylating agents.

A new group of steroidal alkylating agents has been synthesized for potential anticancer activity. The compounds contain a sulfonic ester, a mono- or a bifunctional nitrogen mustard function attached to an ethyl chain and forming ether linkages at the 3- or 17 beta-position of the steroids selected. The products were tested for their in vitro anabolic and catabolic properties by measuring their effects on the bovine pancreatic ribonuclease.

Alkylating Agents↗

Effects of drugs associated with hyperprolactinemia on plasma steroids and on steroid receptors and metabolism in human breast cancer.

Certain commonly taken pharmaceutical preparations induce increased levels of plasma prolactin. The effects of these drugs on (a) tumor steroid receptors and metabolism, and (b) plasma hormones and hormone binding proteins have been studied in postmenopausal women with breast cancer. Two groups have been compared, 18 patients on drug treatment for at least 2 months and 15 subjects with no history of drug ingestion. Patients taking medication had significantly higher levels of plasma prolactin compared with control women. No significant difference was observed between the groups with regard to the plasma concentrations of dehydroepiandrosterone (DHA) and its sulphate (DHS), testosterone, estrone, estradiol-17 beta, sex hormone binding globulin (SHBG), and albumin. Similarly, no difference was observed between these two groups with regard to estrogen receptor (ER), progestogen receptor (PR), or androgen receptor (AR) levels in the tumors nor their ability to metabolize (7(-3)H) testosterone. It is considered that the ingestion of these drugs does not affect tumor mechanisms involving steroids.

Aged↗

Dermatosis in magnesium-deficient hairless rats: effects of steroidal and non-steroidal anti-inflammatory drugs.

Dermatosis in magnesium-deficient hairless rats has been described as a reproducible model of skin inflammation. It was therefore felt of interest to search for the effects of various anti-inflammatory compounds on this model. Results showed that 1) Dexamethasone acetate completely abolished the rash, 2) Indomethacin, a Non-Steroidal Anti-Inflammatory Drug (NSAID), inhibitor of the cyclooxygenase pathway was quite inactive, 3) Benoxaprofen, a NSAID inhibitor of both cyclooxygenase and lipoxygenase pathways only slightly modified the development of the pathology. Activity of steroidal anti-inflammatory drugs on this model may be related to their immunosuppressive effects.

Animals↗