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  • 1
    Digitale Medien
    Digitale Medien
    s.l. : American Chemical Society
    Macromolecules 27 (1994), S. 6956-6962 
    ISSN: 1520-5835
    Quelle: ACS Legacy Archives
    Thema: Chemie und Pharmazie , Physik
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 82 (1997), S. 2359-2364 
    ISSN: 1089-7550
    Quelle: AIP Digital Archive
    Thema: Physik
    Notizen: (Ba,Sr)TiO3 (BST) thin films grown by chemical vapor deposition and with platinum (Pt) top and bottom electrodes have been characterized with respect to the leakage current as a function of temperature and applied voltage. The data can be interpreted via a thermionic emission model. The Schottky approximation accounts for superohmic behavior at higher fields, but the barrier lowering is stronger than expected from this theory. While the leakage mechanism is comparable to SrTiO3 thin films prepared by chemical solution deposition, the absolute values of the leakage current are significantly lower for the metalorganic chemical vapor deposition (MOCVD) prepared BST film. This is presumably due to a more homogeneous microstructure of the latter and may also be due to different electrode processing. The influence of the film thickness on the leakage in combination with additional findings is used to discuss the field distribution in the films under a dc voltage stress. © 1997 American Institute of Physics.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: We have previously shown that progesterone (PROG) is synthesized by Schwann cells and promotes myelin formation in the peripheral nervous system (PNS). We now report that this neurosteroid also stimulates myelination in organotypic slice cultures of 7-day-old (P7) rat and mouse cerebellum. Myelination was evaluated by immunofluorescence analysis of the myelin basic protein (MBP). After 7 days in culture (7DIV), we found that adding PROG (2–5 × 10−5 M) to the culture medium caused a fourfold increase in MBP expression when compared to control slices. The effect of PROG on MBP expression involves the classical intracellular PROG receptor (PR): the selective PR agonist R5020 significantly increased MBP expression and the PR antagonist mifepristone (RU486) completely abolished the effect of PROG on this MBP expression. Moreover, treatment of P7-cerebellar slice cultures from PR knockout (PRKO) mice with PROG had no significant effect on MBP expression. PROG was metabolized in the cerebellar slices to 5α-dihydroprogesterone (5α-DHP) and to the GABAA receptor-active metabolite 3α,5α-tetrahydroprogesterone (3α,5α-THP, allopregnanolone). The 5α-reductase inhibitor L685-273 partially inhibited the effect of PROG, and 3α,5α-THP (2–5 × 10−5 M) significantly stimulated the MBP expression, although to a lesser extent than PROG. The increase in MBP expression by 3α,5α-THP involved GABAA receptors, as it could be inhibited by the selective GABAA receptor antagonist bicuculline. These findings suggest that progestins stimulate MBP expression and consequently suggest an increase in CNS myelination via two signalling systems, the intracellular PR and membrane GABAA receptors, and they confirm a new role of GABAA receptors in myelination.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Progesterone provides neuroprotection after spinal cord injury, but the molecular mechanisms involved in this effect are not completely understood. In this work, expression of two binding proteins for progesterone was studied in intact and injured rat spinal cord: the classical intracellular progesterone receptor (PR) and 25-Dx, a recently discovered progesterone membrane binding site. RT-PCR was employed to determine their relative mRNA levels, whereas cellular localization and relative protein levels were investigated by immunocytochemistry. We observed that spinal cord PR mRNA was not up-regulated by estrogen in contrast to what is observed in many brain areas and in the uterus, but was abundant as it amounted to a third of that measured in the estradiol-stimulated uterus. In male rats with complete spinal cord transection, levels of PR mRNA were significantly decreased, while those of 25-Dx mRNA remained unchanged with respect to control animals. When spinal cord-injured animals received progesterone treatment during 72 h, PR mRNA levels were not affected and remained low, whereas 25-Dx mRNA levels were significantly increased. Immunostaining of PR showed its intracellular localization in both neurons and glial cells, whereas 25-Dx immunoreactivity was localized to cell membranes of dorsal horn and central canal neurons. As the two binding proteins for progesterone differ with respect to their response to lesion, their regulation by progesterone, their cellular and subcellular localizations, their functions may differ under normal and pathological conditions. These observations point to a novel and potentially important role of the progesterone binding protein 25-Dx after injury of the nervous system and suggest that the neuroprotective effects of progesterone may not necessarily be mediated by the classical progesterone receptor but may involve distinct membrane binding sites.
    Materialart: Digitale Medien
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  • 5
    ISSN: 1520-5835
    Quelle: ACS Legacy Archives
    Thema: Chemie und Pharmazie , Physik
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 6
    ISSN: 1520-5835
    Quelle: ACS Legacy Archives
    Thema: Chemie und Pharmazie , Physik
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 7
    ISSN: 1365-2826
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: The gonadal steroids estradiol and progesterone have previously been shown to modulate the specific binding of the GABAA agonist, [3H]muscimol, in the CA1 region of the hippocampus, the ventromedial nucleus of the hypothalamus and the midbrain central gray of ovariectomized female rats. In this report we show a sex difference in the level of binding in the very caudal ventromedial nucleus of the hypothalamus. In contrast to females, there is no steroid modulation of [3H]muscimol binding in the ventromedial nucleus of the hypothalamus and midbrain central gray of males. These effects may be functionally related to GABAergic control of female sexual behavior. In contrast, steroid modulation of [3H]muscimol binding in the CA1 region of the hippocampus occurred to the same degree in males and females, and there was no difference in the level of binding in any region of the hippocampus between gonadectomized males and females.Incubation of brain slices with progesterone or its metabolite 5α-3α-pregnanolone dissolved in ethanol, produced a significant increase in [3H]muscimol binding in most brain regions as compared to control brain slices treated with ethanol alone. Moreover, there was also a marked increase in [3H]muscimol binding in all brain areas in the control condition which contained 100 mM ethanol, as compared to brain slices not preincubated with ethanol. The increase in binding after in vitro treatment with either progesterone or 5α-3α-pregnanolone is notably different from that seen after progesterone given in vivo 4 h prior to assay in that it is not site-specific, does not depend on prior treatment with estradiol and shows no sex difference. These results suggest different mechanisms for progesterone effects on the GABAA receptor when administered in vivo as compared to in vitro.
    Materialart: Digitale Medien
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  • 8
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neuroendocrinology 2 (1990), S. 0 
    ISSN: 1365-2826
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: The activity of three testosterone-metabolizing enzymes (aromatase, 5α-reductase and 5β-reductase) was determined in the quail brain using the Palkovits punch technique combined with a very sensitive radioenzyme assay. Sex differences and the effects of gonadectomy and testosterone treatment on the activity of the three enzymes were quantified in eight brain nuclei which are implicated in the control of various aspects of reproductive behavior and physiology. The aromatase was only present in a few brain areas in which its activity was strongly controlled by testosterone. In two brain regions (medial preoptic nucleus and preoptic area in general) the activity of the enzyme was higher in males than in females. These sex differences disappeared in gonadectomized birds and in gonadectomized birds treated with testosterone, suggesting that they might only result from different circulating steroids in both sexes. However, in the posterior part of the medial preoptic nucleus, there was a strong tendency for the induction of aromatase by testosterone to be larger in males than in females. This supports our earlier finding that in the preoptic area, the aromatase activity is sexually differentiated. This difference probably has a restricted neuroanatomical localization and could only be demonstrated by more precise anatomical methods such as immunocytochemistry. The two testosterone reductases (5α and 5β) showed a more homogeneous distribution in the brain. They were not affected by the hormonal treatments or the sex of the birds except for the 5β-reductase which was significantly more active in three brain nuclei of the females (ventromedial nucleus of the hypothalamus, area hypothalamica lateralis and tuber) by comparison with the males. These sex differences were maintained irrespective of the hormonal status of the birds suggesting that they might be organizational in nature. The relation of these enzymes and their regulation to the control of reproduction is discussed and the usefulness of this approach combining punch technique and radioenzyme assay is evaluated.
    Materialart: Digitale Medien
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  • 9
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neuroendocrinology 3 (1991), S. 0 
    ISSN: 1365-2826
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: A variable amount of circulating testosterone that reaches brain cells is converted to biologically inactive 5β-reduced metabolites, namely, 5β-dihydrotestosterone (5β-DHT) and 5β-androstane-3α,17β-diol (5β,3α-diol). In avian species, the production of inactive 5β-DHT and 5β,3α-diol is highest during embryonic and post-hatching life. In the present study, we have investigated the possibility that 5β-reduction may not only correspond to a steroid inactivation pathway, but that 5β-reduced metabolites of testosterone may exert direct inhibitory effects on enzymatic pathways producing biologically active steroids. When added to hypothalamic homogen-ates prepared from adult male doves, 5β-DHT but not 5β,3α-diol inhibits the activity of the aromatase enzyme, which converts testosterone to 17β-oestradiol. During the first days after hatching, when the production of 5β-reduced metabolites is high, the hypothalamic aromatase is also inhibited by 5β-DHT. We conclude that a high 5β-reductase activity during sensitive periods for sexual differentiation may protect the avian brain from the differentiating effects of circulating androgens by inhibiting the production of oestrogen.
    Materialart: Digitale Medien
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  • 10
    ISSN: 1460-9568
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Steroids which are synthesized within the nervous system, such as progesterone, have been termed ‘neurosteroids’. Levels of progesterone are much larger in peripheral nerves of rats and mice than in plasma, and persist after removal of the steroidogenic endocrine glands. Schwann cells are a source of progesterone: when isolated from embryonic dorsal root ganglia, they can synthesize progesterone from pregnenolone, the obligate precursor of all steroids. Locally produced progesterone has been shown to play an important role in myelination of peripheral nerve. We show here that sensory neurons from embryonic dorsal root ganglia also express 3β-hydroxysteroid dehydrogenase and can convert [3H]pregnenolone to [3H]progesterone. Moreover, when cultured under different conditions and incubated for 24 h in the presence of 100 nM [3H]pregnenolone, they produce 5–10 times more [3H]progesterone than Schwann cells. The conversion of pregnenolone to progesterone by neurons is further increased by a diffusible factor produced by Schwann cells. Sensory neurons can also metabolize progesterone to 5α-dihydroprogesterone, but unlike Schwann cells, they do not produce 3α,5α-tetrahydroprogesterone, a potent positive allosteric modulator of γ-aminobutyric acid type A receptors. We also show that cells isolated from the adult nervous system still have the capacity to convert [3H]pregnenolone to progesterone and its 5α-reduced metabolites: neurons and Schwann cells purified from dorsal root ganglia of 6 week old male rats show a similar pattern of pregnenolone metabolism to cells isolated from 18 day old embryos. These findings further support the important role of progesterone in the development and regeneration of the peripheral nervous system.
    Materialart: Digitale Medien
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