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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 10 (1998), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The immortalized hypothalamic neuronal cell lines GT1-1 and GT1-7 represent unique model systems to investigate the physiological control of gonadotropin-releasing hormone (GnRH) secretion.Using immunofluorescence microscopy, key proteins of regulated exocytosis, e.g. synaptotagmin, synaptobrevin and SNAP-25 (synaptosomal associated protein of 25 kDa) were found in GT1 neurons. In addition, GT1 neurons contained synaptophysin, a marker protein for small synaptic vesicles (SSVs) which are responsible for the storage of neurotransmitters such as γ-aminobutyric acid (GABA). Upon subcellular fractionation, a lighter vesicle population characterized by synaptophysin separated from a denser vesicle population containing GnRH. Both vesicle populations contained synaptobrevin and synaptotagmin. Besides GnRH, GT1 neurons expressed glutamic acid decarboxylase at the mRNA-level and synthesized GABA. More importantly, GT1 neurons took up and stored 3H-GABA. The stored GABA was released after stimulation with increasing K+ concentrations and by α-latrotoxin. Reducing the extracellular Ca2+-concentration abolished stimulated secretion, indicating that GABA was released by regulated exocytosis. Hormone secretion from GT1 neurons is controlled by GABA via GABAA and GABAB receptors reflecting the situation in vivo.Our data provide the first evidence that GT1 neurons possess a second regulated secretory pathway sustained by SSVs storing and releasing GABA. The released GABA influences GnRH secretion by an auto- or paracrine loop.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Molecular and Cellular Endocrinology 97 (1993), S. 153-158 
    ISSN: 0303-7207
    Keywords: (GnRH) ; (PCR) ; Competitive polymerase chain reaction ; Gonadotropin-releasing hormone ; Micropunch ; Preoptic area ; mRNA
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1434-0879
    Keywords: Prostate-specific antigen ; ELISA ; Clinical validation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary PSA is an important tumor-marker for prostatic cancer disease. We developed a sensitive, simple and inexpensive Sandwich ELISA for PSA with two monoclonal antibodies. The precision and reliability of the assay are reflected in the low inter-and intraassay coefficient of variation. PSA was not detectable in sera from normal females (n=50). Sera from males with different serum levels of PSA (normal males, patients with prostate hypertrophy, prostate cancer patients, n=79) and 15 prostate cancer patients treated with Zoladex were measured by our ELISA and by a commercially available RIA. The correlation coefficient between these both testsystems was close to 1 (r=0.97).
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1076
    Keywords: Key words Thalassaemia major ; Growth hormone ; Neurosecretory dysfunction ; Androgen priming ; Gonadotropins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In patients with β-thalassaemia major, frequent blood transfusions combined with desferrioxamine chelation therapy lead to an improved rate of survival. Endocrine disorders related to secondary haemosiderosis such as short stature, delayed puberty and hypogonadism are major problems in both adolescent and adult patients. A total of 32 patients with β-thalassaemia major undergoing treatment at the Children's Hospital, University of Göttingen were examined. Fourteen of these were short in stature. Growth hormone (GH) secretion was investigated in 13 patients exhibiting either a short stature or reduced growth rate. The stimulated GH secretion of 10 patients in this subgroup lay within the normal range. Studies of their spontaneous GH secretion during the night revealed that these patients had a markedly reduced mean GH and reduced amplitudes in their GH peaks. Low insulin-like growth factor (IGF)-I levels were seen in the growth-retarded thalassaemic patients. Eight were subjected to an IGF generation test and showed a strong increase in both IGF-I and insulin-like growth factor binding protein (IGFBP)-3 levels indicating intact IGF-I generation by the liver. Hypogonadotropic hypogonadism was found to be present in both the male and female patients with impaired sexual development. After priming with LH-releasing hormone (GnRH) per pump in 2 female and 5 male patients, no change in either their serum oestradiol or testosterone levels or in LH/FSH response to GnRH was observed suggesting that they were suffering from a severe pituitary gonadotropin insufficiency. Three male patients at the age of puberty but exhibiting short stature, low GH, low IGF-I and hypogonadism received low dose long-acting testosterone. After 3–12 months of therapy there was a marked growth spurt, higher nocturnal GH levels and an increase in both IGF-I and IGFBP-3. Conclusion Reduced GH secretion and low IGF-I in thalassaemic patients are related to a neurosecretory dysfunction due to iron overload rather than to liver damage. Hypogonadotropic hypogonadism is caused by the selective loss of pituitary gonadotropin function. In patients with both GH deficiency and hypogonadism, low dose sexual steroid treatment should be considered either as an alternative or an additional treatment before starting GH therapy.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1438-2199
    Keywords: Amino acids ; Taurine ; Prolactin ; Dopamine ; GABA ; HPLC ; Hypothalamus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Taurine (Tau), a putative inhibitory amino acid neurotransmitter, has been shown to stimulate prolactin (PRL) release. Using ovariectomized, estrogen-replaced adult rats we investigated initially the effect of this amino acid, injected by different routes, on PRL secretion in vivo. Tau (100–500 mg/kg) had no effect on PRL release when given i.p.; 15 min after i.c.v. injection of Tau (3μmoles), a significant increase in serum PRL levels was observed (78 ± 9 ng/ml over basal levels, p 〈 0.01 vs. controls). In vitro (cultured anterior pituitary cells) PRL release was not affected by a 5 h incubation with Tau (10−3–10−8 M). Basal dopamine (DA) or gamma-aminobutyric acid (GABA) output from superfused mediobasal hypothalamic fragments (MBH) was not affected by Tau (10−3 M or 10−5 M). However, during stimulation with KCl (50mM), Tau (10−3 M) significantly lowered DA release, and increased GABA output. It is concluded that Tau acts at a central level to increase PRL secretion, most probably by modulating the hypothalamic release of neurotransmitters controlling lactotroph function.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Reproduktionsmedizin 14 (1998), S. 106-114 
    ISSN: 1434-808X
    Keywords: Schlüsselwörter Adenohypophyse ; LH- und Prolaktin-Pulse ; Kopulsatilität ; parakrine Kopplung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zusammenfassung Die Sekretion der Hypophysenhormone LH und Prolaktin wird durch hypothalamische Neurone, die Relasing- (GnRH, PRF) und Inhibiting-Faktoren (PIF) freisetzen, kontrolliert. Entscheidend für die Stimulation der LH-Sekretion ist die pulsatile Freisetzung des GnRH aus dem Hypothalamus („hypothalamischer GnRH-Pulsgenerator“). Der GnRH-Pulsgenerator induziert eine pulsatile LH-Sekretion. In dieser Übersicht wird die Freisetzungsdynamik von LH und Prolaktin verglichen. Die offenkundige Kopulsatilität von LH- und Prolaktin wird hinsichtlich ihrer Kontrolle und der biologischen Bedeutung diskutiert. Die Schlußfolgerungen sind: 1. Durch Streßeinfluß wird die Prolaktinsekretion rasch, aber schnell adaptierbar, stimuliert. Diese vermehrte Prolaktinausschüttung ist nicht mit einer Gonadotropinausschüttung assoziiert. Der auslösende hypothalamische Mechanismus ist eine veränderte PRF- oder PIF-Sekretion. 2. GnRH-induzierte LH-Pulse sind von Prolaktinpulsen begleitet. Diese Pulse werden auf hypophysärer Ebene koordiniert, indem GnRH die Freisetzung eines parakrin wirkenden PRF stimuliert. 3. Durch die gleichzeitige Ausschüttung von Prolaktin wird die luteotrope Wirkung von LH ermöglicht. 4. Aufgrund des pulsatilen Sekretionsmusters und der Stimulation durch Streß sollten erhöhte Prolaktinwerte durch mehrfache Blutentnahmen abgesichert werden. Dauerhaft erhöhte Prolaktinwerte weisen auf ein Prolaktinom hin.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Reproduktionsmedizin 15 (1999), S. 173-178 
    ISSN: 1434-808X
    Keywords: Schlüsselwörter Pestizide ; Phytoestrogene ; Plastik ; Umwelt ; Karzinome ; Key words Pesticides ; Insecticides ; Environment ; Cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The definition of endocrine disrupters is not very sharp. At present all non-physiologic substances which bind to steroid receptors, are defined as endocrine disrupters of which the best studied are estrogenic in nature. Many pesticides or insecticides or their metabolites have estrogenic activity and pollute our surface water. Here they may cause severe estrogenization of aquatic life. Only traces of these substances are demonstrable in drinking water. On the other hand, weak estrogens present in plastic ware may be ingested by men and therefore be potentially harmful for human health. On the other hand, many plants produce socalled‚hyto-estrogens’, particularly soy products are rich in phyto-estrogens but their high consumption in Asian populations are most likely the reason for reduced occurrence of breast cancer. Many plant extracts used for human medication also contain phyto-estrogens and are beneficial in the treatment of climacteric complaints. Hence, not all endocrine disruptors must be harmful to human health, in fact, some of them (clearly phyto-estrogens) may have beneficial effects.
    Notes: Zusammenfassung Die Definition für „endocrine disrupter“ ist sehr unscharf. Zur Zeit werden alle körperfremden Substanzen, welche an Steroidrezeptoren binden oder diese inhibieren, als endocrine disrupters betrachtet. Die meisten Grundlagen und klinischen Studien beschäftigen sich mit estrogenen Wirkungen von endocrine disrupters. Viele Pestizide und Insektizide sowie deren Metabolite haben estrogene Wirkungen und kommen naturgemäß in recht hohen Konzentrationen in unsere Oberflächengewässer. Hier üben sie in zahlreichen aquatischen Spezies femininisierende Wirkungen aus. Das Trinkwasser für menschlichen Gebrauch stammt überwiegend aus dem Grundwasser, wo diese Xenoestrogene in nicht nennenswertem Umfang nachgewiesen wurden. Für die menschliche Gesundheit dagegen können Phthalate und Bisphenole, ebenfalls schwache Estrogene, eine Rolle spielen. Sie werden in der Verpackungsindustrie bei der Plastikherstellung in großen Mengen eingesetzt. Eine weitere Quelle für Xenoestrogene stellen Pflanzen dar. Fast jede Pflanze produziert Isoflavone in mehr oder weniger großen Mengen, welche ebenfalls sogenannte Phytoestrogene sind. Besonders reich an Phytoestrogenen sind Sojaprodukte. Die Tatsache, daß asiatische Populationen, deren Proteingehalt überwiegend durch Sojaprodukte gedeckt wird, weniger Mammakarzinome entwickeln, hat zu der Annahme geführt, daß diese Phytoestrogene die Mammakarzinomentwicklung hemmen. Andererseits sind die aus Industriechemikalien beschriebenen Xenoestrogene in höheren Konzentrationen bei Patientinnen mit Mammakarzinom nachgewiesen worden. Die Beschreibung eines zweiten Estrogenrezeptortypen und zahlreicher Splicingvarianten kann möglicherweise organselektive Wirkungen von Xenoestrogenen verständlich machen. Phytoestrogene kommen in zahlreichen Pflanzenextrakten vor, die zur Therapie klimakterischer Beschwerden Einsatz finden.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Reproduktionsmedizin 15 (1999), S. 405-409 
    ISSN: 1434-808X
    Keywords: Schlüsselwörter Estrogenrezeptoren ; Knochen ; Arteriosklerose ; Endometrium ; Zentralnervensystem ; Key words Estrogen receptors ; Bone ; Arteriosclerosis ; Endometrium ; Central nervous system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Almost each cell in the body is estrogen-receptive. The strength of estrogen influence on organs or organ systems, however, may vary. Thus, estrogen withdrawal may have more or less severe pathophysiological consequences. Recently, the existence of two estrogen receptors has been established (estrogen receptor α and β = ERα and ERβ and several splice variants of these two basic receptor types have been desribed). This, together with our increasing knowledge about tissue-specific enhancer and repressor genes now allows a better understanding of the organ-specific effects of estrogens. In view of gynecological endocrinology, hormone replacement therapy with estrogens is beneficial for most organs in the body (bone, cardiovascular system, CNS). However, pure estrogen therapy may have deleterious effects in the endometrium of the uterus because it may initiate the development of uterine cancer. In the uterus of most species studied so far, no ERβ but only the classical ERα gene has been described. Hence, drug companies have now intensively begun to search for ERβ-specific estrogens. The first, relatively specific, non-steroidal product that addresses primarily the ERβ is the drug raloxifen, which has been recently introduced clinically. However, also some natural phyto-estrogens appear to be ERβ-specific.
    Notes: Zusammenfassung Fast jede Körperzelle ist estrogenrezeptiv. Es gibt allerdings Organe und Organsysteme, die besonders unter dem Einfluß von Estrogenen stehen und die sich bei Estrogenmangel krankhaft verändern können. Die vielfältigen Wirkungen von Estrogenen konnten nicht vollständig verstanden werden, solange die Existenz von nur einem Estrogenrezeptor quasi ein Dogma war. Erst die Klonierung eines zweiten (Estrogenrezeptor β = ERβ) sowie das bessere Verständnis von gewebespezifischen Enhancer- und Repressor-Genen konnten die vielfältigen und z. T. organspezifischen Wirkungen der Estrogene aufklären. Aus der Sicht der gynäkologischen Endokrinologie ist die Hormonersatztherapie mit Estrogenen für fast alle Organe des Körpers (Knochen, Herz-Kreislauf-System, Zentralnervensystem) segensreich. Eine nicht gestagenbegleitete Estrogentherapie kann allerdings verheerende Folgen am Endometrium mit Entwicklung eines Corpus-Karzinoms haben. Da der Uterus praktisch kein ERβ sondern nur den klassischen ERα exprimiert, hat eine intensive Suche nach ERβ-spezifischen Estrogenen begonnen. Ein erstes, halbwegs spezifisches nicht-steroidales Produkt scheint das kürzlich in die Klinik eingeführte Raloxifen zu sein, aber auch einige Phytoestrogene scheinen ERβ-spezifisch zu wirken.
    Type of Medium: Electronic Resource
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