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  • Fetal face syndrome  (1)
  • Inhibition of androgen binding  (1)
  • Renales  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 64 (1986), S. 732-737 
    ISSN: 1432-1440
    Keywords: Human fibroblasts ; Androgen binding ; Inhibition of androgen binding ; Steroids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ability of various natural and synthetic steroids (some of which are widely used in clinical practice) to compete with dihydrotestosterone receptor binding in human genital skin fibroblasts was studied. Binding was assessed in fibroblast monolayers after incubation for 1 h at 37 °C with 2 nM 3H-dihydrotestosterone in the presence or absence of increasing concentrations of the steroid to be tested. Inhibition constants (Ki) were determined as the concentration of competitor-required for 50% inhibition of3H-dihydrotestosterone binding. In addition, relative binding activity (RBA) of each test compound was calculated. Each competitor was tested in at least two different cell strains. The concentrations of unlabeled methyltrienolone (a synthetic nonmetabolizable androgen) and dihydrotestosterone for 50% inhibition of3H-dihydrotestosterone binding were in the same order of magnitude, namely, 2 nM (2.2 respectively, 2.4 nM), whereas the affinity of testosterone was approximately one-fifth that of dihydrotestosterone. Other potent competitors for dihydrotestosterone binding were three progestins (norgestrel, gestoden, and medroxyprogesterone acetate) which have Ki values similar to testosterone. An order of magnitude lower Ki values (around 10−7 M) were found for the androgen 17α-propylmesterolone, the antiandrogen cyproterone acetate, and the progestin norethisterone acetate. Binding affinities of all other steroids to the androgen receptor were markedly lower and showed the following order of potency: estrogens (estradiol, ethinyl estradiol, diethylstilbestrol) 〉 glucocorticoids as well as aromatase inhibitors and potassium canrenoate. We conclude that (a) among the compounds tested some progestins are very potent in their ability to interact with human skin fibroblast receptors and thus may affect endogenous androgen action; (b) estrogens are relatively weak androgen receptor binders; and (c) this receptor assay in combination with pharmacokinetic and metabolic studies appears to be a useful screening test to evaluate the potency of various steroids for androgen and antiandrogen therapy.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1076
    Keywords: Robinow syndrome ; Fetal face syndrome ; Androgen receptor deficiency ; Persistence of Mullerian ducts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Typical features of the “fetal face” or Robinow syndrome are reported in a male infant who presented with ambiguous genitalia and persistence of the Mullerian ducts. Histology of the testes was normal whereas endocrinological studies showed partial deficiency of androgen receptors.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1591-9528
    Keywords: Mean arterial blood pressure ; Heart rate ; Renal transport system ; Mittlerer arterieller Blutdruck ; Herzfrequenz ; Renales ; Transportsystem
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei Ratten, die mit Furosemid oder Mefrusid vorbehandelt worden waren, wurde über einen Zeitraum von 2 Std die Wirkung von intraperitoneal injiziertem Guancydin (25 mg/kg) auf den mittleren arteriellen Blutdruck und die Herzfrequenz beobachtet. Im Vergleich zu nichtvorbehandelten Tieren konnte eine deutliche Potenzierung der blutdruck- und herzfrequenzreduzierenden Guancydinwirkung nachgewiesen werden. Der Effekt war dosisabhängig, da 2 Std nach der Guancydingabe die mit 25 mg/kg Furosemid oder 50 mg/kg Mefrusid vorbehandelten Tiere einen signifikant niedrigeren Blutdruck aufwiesen als diejenigen, die vorher 12,5 mg/kg Furosemid oder 25 mg/kg Mefrusid erhalten hatten (p〈0,01). Es konnte wahrscheinlich gemacht werden, daß die Ursache für diesen Effekt weniger in einer diuretikumbedingten Veränderung des Wasser- und Elektrolythaushalts als darin liegt, daß Furosemid, Mefrusid und Guancydin über dasselbe renale Transportsystem ausgeschieden werden. Als Ausdruck einer Konkurrenz der Substanzen um dieses Transportsystem kam es möglicherweise zu einer Verzögerung der Guancydinausscheidung und somit zu einer verstärkten Wirkung des Antihypertensivums auf den Blutdruck und die Herzfrequenz. Diese Auslegung der Ergebnisse wird außerdem dadurch bestätigt, daß in weiteren Versuchen der diuretische und natriuretische Furosemideffekt durch Vorbehandlung mit Guancydin signifikant herabgesetzt werden konnte (p〈0,01). Dieser Effekt war gleichfalls dosisabhängig.
    Notes: Summary In rats, which were treated, with furosemide and mefruside, the effect of intraperitoneally injected guancydine (25 mg/kg) on the mean arterial blood pressure and the heart rate was studied over a period of 2 hrs. In comparison with, normal animals, a significant potentiation of the depressant effect of guancydine on heart rate and blood pressure was observed. This effect was dose dependent, since the animals, which were pretreated with 25 mg/kg furosemide or 50 mg/kg mefruside, showed a significantly lower blood pressure than rats, which received 12,5 mg/kg furosemide or 25 mg/kg mefruside (p〈0.01). It is suggested, that the causes of these effects were not the saluretic-induced alterations of the water and electrolyte balance but the fact, that furosemide, mefruside and guancydine are excreted by the same renal transport system. These findings were strongly supported by the fact, that in other experiments pretreatment with guancydine significantly lowered the diuretic and natriuretic action of furosemide (p〈0.01). This effect was also dose dependent.
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